Keywords: Mosquitoes
“Target species complex” concept: Strengthening environmental risk assessment of engineered gene drives
35531J.B. Connolly, Y. Devos, D.C.M. Glandorf, and J. Romeis, Proc. Natl. Acad. Sci., 2026-03-30 19:11:30.
The recent opinion piece of Christophe Boëte critiqued the concept of the target species complex (TSC) in environmental risk assessment (ERA) of engineered gene drives (EGDs) (1). While constructive debate is essential, the piece misrepresents the purpose of TSC and conflates unrelated mechanisms, creating misconceptions that merit clarification. Malaria-transmitting mosquitoes often belong to species complexes, comprising vector and nonvector species, where hybridization can be detected in laboratory settings and occasionally in the field (2–4). Low-threshold EGDs are self-sustaining and nonlocalizing (5). Should such EGD be released in a species complex where target genomic sequences are conserved, in the event of interspecific mating in the field vertical gene drive transfer (VGDT) to nonvector species could occur, potentially harming biodiversity protection goals. Conversely, VGDT to vector species could advance health objectives (6).
As mosquitoes go year-round in L.A., a promising fix hits a snag
35516Lila Seidman, Los Angeles Times, 2026-03-23 09:06:38.
Residents were supposed to get a respite from the ankle-nipping mosquitoes that fueled a recent surge in dengue fever in Los Angeles County. Typically, the invasive mosquitoes — called Aedes aegypti — essentially disappear from winter until early May in the region. Instead, complaints to local agencies tasked with controlling the pests spiked recently. “We have not seen them go away altogether like they have in previous years,” said Susanne Kluh, general manager for the Greater Los Angeles County Vector Control District. Their unusual presence adds to the urgency of work going on in a 40-foot shipping container tucked away in Pacoima. It's about to transform into a bustling nursery for tens of thousands of mosquitoes. This May, the district is set for the third year in a row to release legions of sterilized male mosquitoes — which don't bite — into parts of Sunland-Tujunga. The last two years were promising, with the female population in two treated neighborhoods plunging by an average of more than 80%. Yet business owners have signaled they're not willing to pay to expand it. That's thrown uncertainty into officials' goal of eventually bringing the approach to their whole service area, spanning 36 cities and unincorporated communities. “Unfortunately, that's going to be a rather expensive endeavor,” said Steve Vetrone, an assistant general manager for the district. “I can tell you right now that's not something that we can do with our current operating budget.”
Liverpool School of Tropical Medicine joins the Target Malaria Consortium
35499Dr. Tony Nolan, Target Malaria: News, 2026-03-10 09:34:21.
Target Malaria has so far been working on the three widespread vectors of the Anopheles gambiae species complex: An. coluzzii, An. gambiae, and An. arabiensis. As members of a species complex, these three species are morphologically indistinguishable. Together, they are among the most important malaria vectors in sub-Saharan Africa. Although they are distinct species, they can occasionally inter-breed. In addition, Anopheles funestus is a widespread vector across sub-Saharan Africa. It is more distantly related to the gambiae species complex and is not capable of hybridising with those species. An. funestus has distinct ecological characteristics and is a highly efficient vector of malaria – its species name, funestus, means “deadly”. In some areas, it is the dominant contributor to malaria transmission. Modelling indicates that achieving the full public health impact of gene drive will require trageting of An. funestus, as malaria transmission in many regions is shared between multiple vector species. Anopheles funestus is particularly challenging to colonise and maintain in the laboratory. Our team at the Liverpool School of Tropical Medicine was among the first to demonstrate stable genetic modification of An. funestus, establishing the technical foundation required to explore gene drive approaches in this species. Through joining Target Malaria, we will extend gene drive research beyond the gambiae complex and support the development of multi-species gene drive strategies for malaria control.
Compound effector genes suppress malaria parasite infections in gene-drive population modification strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii
35494Rebeca Carballar-Lejarazú, Yuemei Dong, Thai Binh Pham, et al., G3 Genes|Genomes|Genetics, 2026-03-09 10:43:52.
Malaria remains a major global health burden and is caused by protozoan parasites in the genus Plasmodium. Parasites are transmitted to humans during blood feeding by anopheline mosquitoes, and members of the Anopheles gambiae species complex are important vectors in sub-Saharan Africa. Gene-drive technologies offer promising options for disease control by enabling the spread of genetic traits through mosquito populations that block parasite transmission. We report here the development and characterization of four population modification gene-drive strains in Anopheles gambiae s.s. and An. coluzzii carrying compound effector genes. We sought to enhance the effectiveness of existing gene-drive strains to block Plasmodium transmission, thereby reducing vector competence and minimizing the opportunities for selection of resistant parasites. Two compound effector gene modules, TP24 and TP43, were introduced using Cas9 endonuclease and dual guide RNAs into TP13-based gene-drive strains to produce the An. gambiae AgTP24 and AgTP43 strains. The gene-drive cassettes were then introgressed into An. coluzzii to produce AcTP24 and AcTP43. Gene-drive dynamics, gene conversion, and inheritance were high in all strains, with 95% to 100% inheritance of the gene-drive constructs. Life table analyses showed mixed impacts on fitness dependent on the species and copy number (hemi- or homozygosity) of the gene-drive systems. The compound effector molecule gene complexes significantly reduced both parasite prevalence and infection intensities in An. gambiae and An. coluzzii following challenge assays with the human malaria parasite, P. falciparum. These findings highlight the potential of compound effector strategies in gene-drive systems to achieve durable malaria transmission control.
Advances in male sex separation for the support of mosquito control programs
35526Duman-Scheel M, Frontiers in Insect Science, 6. 2026-03-09 09:05:10.
Several mosquito control technologies, including the sterile insect technique (SIT), the incompatible insect technique (IIT), and a variety of genetic technologies are emerging as promising solutions for combatting insecticide resistance and the spread of vector-borne diseases. These approaches involve mass releases of male mosquitoes in an effort to suppress mosquito populations in an eco-friendly manner. At small scale, male mosquito selection can be achieved through the use of mechanical separation techniques, but such methods are not sufficient for scaled implementation of emerging mosquito population control technologies. This review discusses mechanical, genetic, and automated mosquito sex sorting techniques that have emerged to address the need for scaled male mosquito production, as well as the potential contributions of RNA interference (RNAi) to facilitate this process. One RNAi method utilizes the oral delivery of yeast expressing interfering RNA targeting genes required for female larval survival. The yeast, which can be incorporated into normal insect larval diets, enables male sex selection during larval rearing in mosquitoes and could easily be extended to other insects. RNAi-mediated sex-sorting technologies, in combination with mechanical, genetic, and automated sorting technologies, could facilitate the scaled production of adult males in support of global insect population suppression efforts.
Wolbachia wMel and wAlbB strains differentially impact the vector competence of Aedes aegypti with a Brazilian genetic background for DENV-1 virus
35484Martins, C.B., David, M.R., Couto-Lima, D. et al., Parasites Vectors, 2026-03-05 08:32:23.
Aedes aegypti mosquitoes infected with the endosymbiotic bacterium Wolbachia pipientis have been released as a sustainable strategy to mitigate arbovirus transmission. Among the strains successfully deployed, wMel and wAlbB have shown promising blocking effects against dengue virus (DENV). However, the strength of viral inhibition depends on Wolbachia density within mosquito tissues, the genetic backgrounds of both host and virus, and the viral dose. In this study, we aimed to investigate the vector competence for DENV-1 of Ae. aegypti with Brazilian genetic background infected with wMel or wAlbB. A total of 493 wild and wMel- and wAlbB-infected mosquitoes were orally challenged with low (5 × 104 FFU/mL) and high (5 × 105) titers of DENV-1. Relative Wolbachia density was measured by quantitative polymerase chain reaction (qPCR), and viral infection in mosquito bodies and saliva was assessed by qPCR with reverse transcription (RT-qPCR). Transmission potential was tested through saliva microinjection into susceptible mosquitoes. The infection prevalence and viral loads in mosquito bodies were analyzed at 7, 14, and 21 days post infection (dpi).Both Ae. aegypti groups infected with wMel and wAlbB had reduced (albeit distinct) DENV-1 infection and transmission relative to wild type mosquitoes. wMel-infected mosquitoes exhibited less abundant bacteria in their bodies but a greater degree of DENV-1 inhibition compared with those carrying wAlbB, indicating that DENV-1 blocking is strain specific rather than Wolbachia density-driven. Moreover, we observed that Wolbachia had a protective effect on mosquitoes by decreasing the DENV-1 loads in their bodies, but with a constant presence of virus. Viral transmission rates in the saliva were similar among wild and wMel- and wAlbB-infected mosquitoes at 7 and 14 dpi but lower in wMel and wAlbB mosquitoes at 21 dpi. The similar DENV-1 loads in mosquito bodies over time (7, 14, and 21 dpi) infected with either the wMel or wAlbB strain, regardless of the viral titer of the infectious blood meal, suggest that Wolbachia may have a maximum pathogen-blocking capacity beyond which additional virus suppression cannot be achieved. The viral suppression only after 21 dpi in the saliva raises concerns and warrants further investigation, as females may transmit before Wolbachia blockage becomes effective. While wAlbB may exhibit comparable DENV-1 blocking to wMel, its enhanced thermal tolerance makes it epidemiologically relevant in tropical regions. Continuous monitoring of Wolbachia dynamics and DENV genomic variation in the field remains essential to evaluate long-term effectiveness and detect potential adaptive viral responses.
Present and Future of Mosquito-Borne Disease Control in Europe with a Specific Focus on the Mediterranean
35535Cholvi, M., Moretti, R., Osório, H. C., et al., Insects, 17. 2026-02-27 19:18:24.
Mosquito-borne diseases are an emerging public health challenge in Europe, driven by the spread of invasive mosquito species capable of sustaining outbreaks of tropical arboviral diseases. Rising temperatures, shifting precipitation patterns, human-driven habitat changes, and prolonged transmission seasons have increased the risk of dengue, chikungunya, and West Nile virus outbreaks, among other vector-borne diseases. Effective control requires a multifaceted approach, combining traditional and novel methods with advanced surveillance technologies and community involvement. However, growing insecticide resistance and concerns about insecticide use highlight the need for more prudent management of current tools and the development of innovative alternatives. Genetic control strategies, including the Sterile Insect Technique (SIT), Wolbachia-based approaches, and genetically modified (GM) mosquitoes, offer promising solutions but still face scientific, regulatory, and societal challenges. This review explores the current landscape of mosquito-borne disease control in Mediterranean Europe, emphasizing key challenges and emerging solutions. An integrated approach that strengthens surveillance, promotes sustainable control methods, and incorporates novel biotechnological tools supported by smart technologies will be essential to reduce the future burden of mosquito-borne diseases in the region.
Ecological analysis of mosquito larval communities in Burkina Faso to inform environmental monitoring of genetic control programs
35470Toé, I., Kientega, M., Lingani, A.J. et al., Scientific Reports, 16. 2026-02-24 14:26:04.
In Burkina Faso, the development of the gene drive technology targeting Anopheles coluzzii raises important ecological questions about potential non-target effects. Understanding interactions in mosquitoes’ natural environments is crucial for developing effective post-release environmental safety monitoring. This study assesses the ecological exposure and potential risks to non-target organisms associated with An. coluzzii suppression. Using co-occurrence, niche overlap metrics, and characterisation of physicochemical parameters, we evaluated interspecific relationships among mosquitoes and macroinvertebrate taxa from larval habitats in Burkina Faso. Combined index revealed distinct ecological relationships, ranging from competitive or facilitative coexistence to spatial segregation driven by predation or behavioural avoidance. Based on these interactions, an exposure score was developed to quantify the potential susceptibility of non-target organisms to ecological changes following the removal of An. coluzzii. The results showed variable exposure among taxa, with An. gambiae s.s. having the highest score, followed by An. arabiensis and Culex spp. Predatory taxa such as Corixidae showed niche overlap but limited spatial co-occurrence, suggesting effective predation. The detection of hybrid forms (An. coluzzii x An. gambiae s.s.) further highlights the potential for gene flow. This study introduces a quantitative framework that combines ecological indices and exposure scores to predict potential risks to non-target organisms.
Advances in CRISPR gene drives for mosquito population control
35449Robyn Raban, Anthony A James, Omar S Akbari, Current Opinion in Microbiology, 90. 2026-02-12 19:25:19.
CRISPR-based gene drive (GD) systems bias allele inheritance during meiosis, enabling transgenes to spread at rates exceeding Mendel’s law of segregation. This capability underlies their potential as powerful tools for controlling mosquito-borne diseases. GDs can be engineered either to suppress mosquito populations or to modify them by introducing traits that block pathogen transmission. Recent advances have focused on improving evolutionary stability, with modeling studies providing insights into expected population dynamics. With a focus on the most current population modification GDs, we discuss advances in GD architectures — including integral and allelic drives, combined modification–suppression systems, and both homing and non-homing toxin–antidote designs — that expand the range of possible strategies and address limitations of early homing drives. Numerous antipathogen effectors with strong pathogen-blocking activity can now be coupled to these systems, with current efforts assessing their durability against genetically diverse pathogens. Key challenges remain, including resistance evolution, ecological impacts, and long-term stability. Nonetheless, GDs offer a promising approach for reducing disease transmission, especially in regions where conventional interventions are difficult to sustain.
Space Coast releases X-rayed skeeters to take bite out of dengue
35410Jim Waymer, Florida Today, 2026-01-29 10:40:25.
The Space Coast has unleashed 'nuked' skeeters in a new biological bid to neuter dengue fever. Last year, Brevard saw its first locally caught cases of the tropical disease and wound up with the most in Florida. In response, the county decided to let loose thousands of X-rayed male mosquitoes to zap the insect's next generation. Turns out an adult skeeter can survive X-ray doses more than 10 times what would kill humans. Unlike humans, once mature, most mosquito cells stop dividing, so radiation rushing through has fewer chances to distort most of its DNA. But X-rays will tear up the insect's reproductive genes enough to render the male mosquito sterile. That's among the reasons mosquito-control officials assure this time-tested method is safe and environmentally friendly. They emphasize that it's not anything like the much-more controversial gene modification of mosquitoes used in recent years in the Florida Keys. "When we're releasing, there's no voodoo," said Joe Faella, Brevard's mosquito control director.
The Genomic Arms Race in Mosquito-Borne Diseases: Integrating Entomopathogenic Fungi, Gene Drive, and Symbiont Technologies for Sustainable Vector Control
35503Rajendran Yamini, Pagalahalli Sankaran Shanmugam, Marimuthu Murugan, et al., J Pure Appl Microbiol., 20:53-65. 2026-01-20 09:32:56.
Mosquito-borne diseases such as malaria, dengue, Zika, chikungunya, and lymphatic filariasis continue to impose enormous health and economic burdens worldwide. The traditional reliance on chemical insecticides has been undermined by the rapid evolution of resistance, ecological concerns, and declining efficacy. Next-generation biocontrol strategies are framed within the concept of a “genomic arms race” between mosquitoes, pathogens, and microbial agents. Entomopathogenic fungi are eco-friendly bioinsecticides with demonstrated efficacy in laboratory, semi-field, and transgenic applications. Symbiont-based approaches, particularly those involving Wolbachia, have been evaluated for their ability to reduce vector competence and spread through populations. Parallel advances in CRISPR-based gene drive technologies have provided transformative tools for population suppression and modification, although their deployment is limited by ethical, ecological, and regulatory concerns. An integrated vector management (IVM) framework combining fungi, gene drives, and symbiont-based tools is proposed as the most promising approach for sustainable mosquito management. This multipronged strategy has the potential to reduce disease transmission, delay resistance development, and minimize ecological disruption, paving the way for resilient, eco-friendly solutions against vector-borne diseases.
Research Advances and Challenges of Gene Drive Technology in Mosquito-Borne Disease Control
35363Yun Jiaqi, Ma Qin, Wang Guandong, et al., Laboratory Animal and Comparative Medicine, 45:773-783. 2026-01-14 12:01:39.
Mosquito-borne diseases (such as malaria, dengue fever, Zika virus disease, and Chikungunya) pose major threats to global public health, while traditional control methods based on chemical pesticides face severe challenges including enhanced drug resistance in vector mosquitoes and environmental pollution. Genetic control strategies have become high-potential alternative solutions for mosquito control due to their species specificity and environmental friendliness. Gene drive technology uses gene editing tools such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) to enable specific genes to efficiently spread in target mosquito populations through "super-Mendelian inheritance", offering a revolutionary strategy for the prevention and control of mosquito-borne diseases. This review systematically summarizes key advances, core challenges, and response strategies of gene drive technology in this field. Research advances: (1) In Anopheles malaria vectors, population suppression drives targeting sex determination genes or female reproductive genes can cause female sterility or skewed sex ratios to achieve population suppression. Population replacement gene drive strategies targeting host genes associated with Plasmodium infection or delivering anti-Plasmodium effector molecules in Anopheles can effectively block pathogen transmission. (2) In Aedes mosquito vectors of arboviruses, targeting female flight-essential genes achieves population suppression, and coupling of antiviral effector systems with drive elements is explored. Optimized split gene drive strategies demonstrate high cutting and recombination efficiency, and models predict safe and controllable spread of disease-resistance traits. (3) In Culex mosquitoes transmitting lymphatic filariasis, homology drive elements are integrated into two genes involved in the eye pigment synthesis pathway, allowing clear visualization of gene drive efficiency through eye color. Core Challenges: technological challenges include low homologous recombination repair efficiency, non-homologous end joining repair causing resistance allele generation, CRISPR/Cas9 off-target effects, and species adaptation differences. Ecological and safety challenges involve gene pool pollution caused by accidental spread of drive elements, potential ecological balance impacts, and long-term irreversible risks. Response strategies and prospects: employing multiplex guide RNA (gRNA) targeting strategies to enhance drive stability and combat potential resistance. Developing reversible designs such as synthetic resistance, reversal drives, and immunizing reversal drives as "genetic brakes". Establishing long-term ecological monitoring systems and mathematical modeling for risk assessment. Exploring "environmentally responsive drives" to enhance controllability. Future research should continuously optimize drive efficiency and specificity, deepen ecological risk evaluation, strengthen international cooperation, and promote ethical consensus and regulatory framework construction, with the aim of making gene drive technology a sustainable prevention and control strategy to address the global health challenge of mosquito-borne diseases under the premise of safety and controllability.
Researchers Use Gene Editing to Separate Male and Female Mosquitoes
35367ISAAA Inc., 2026-01-14 11:04:44.
Researchers from the Hebrew University of Jerusalem have developed a new genetic method to separate male and female mosquitoes, which is highly beneficial for large-scale mosquito control programs. Led by Doron Zaada and Prof. Philippos Papathanos, the study aims to improve existing separation strategies that are labor-intensive, difficult to scale, and rely on releasing only male mosquitoes. The study focused on the Asian Tiger mosquito (Aedes albopictus), a major carrier of diseases such as dengue, chikungunya, and Zika. Using CRISPR, the researchers developed a genetically engineered “Genetic Sexing Strain” by disrupting the mosquito's yellow pigmentation gene, then restored dark pigmentation only in males by linking the gene to nix, a “master switch” that converts females into fertile males. This resulted in a stable strain in which males are dark-colored, and females are yellow. The study also found that the yellow females lay eggs that cannot survive dry conditions, unlike wild mosquito eggs that can survive for months. The genetically converted males were shown to behave and reproduce like natural males, indicating their effectiveness for vector control programs. The researchers said that the next step is to improve the female mosquitoes' ability to survive high temperatures or specific additives used in mosquito mass-rearing biofactories.
Exploratory conversations with biodiversity-oriented civil society groups on the potential applications of gene drive-modified mosquitoes for malaria control in Tanzania
35354Finda, M.F., Sambo, M., Malika, G. et al., Transgenic Res, 35. 2026-01-13 09:53:50.
Gene drive-modified mosquitoes (GDMMs) are gaining attention as sustainable tools to complement existing malaria control strategies. Their ability to self-propagate and spread through wild mosquito populations offers the promise of low-cost, long-lasting impact, but also raises ecological, ethical, and governance concerns. In this evolving debate, civil society organizations (CSOs) are pivotal actors in shaping dialogue, representing community concerns, and influencing policy decisions. This study examined the perspectives and recommendations of biodiversity-oriented CSOs on the governance, testing, and potential application of GDMMs for malaria control in Tanzania. An exploratory qualitative design was employed, involving eight in-depth interviews, one focus group discussion, and three large group discussions with representatives from ten biodiversity-focused CSOs in Tanzania. Participants were selected purposively based on prior involvement in national or regional dialogues related to biotechnology; and the discussions focused on concerns, uncertainties and needs associated with testing and potential use of GDMMs for malaria control, as well as the balance of prospective benefits against long-term environmental risks. Transcripts were analyzed thematically using NVivo 12 Plus. Participants expressed cautious support for research on GDMMs for malaria control but raised concerns about scientific uncertainty, limited local expertise, inadequate transparency, potential transboundary effects and technological dependency. They emphasized the importance of generating robust, context-specific evidence before considering any environmental releases of gene drives; and highlighted concerns over inadequate accountability, particularly the lack of clarity on who would assume responsibility if adverse outcomes arise. They also advocated for early, inclusive, transparent, and continuous engagement with both target communities and the broader public. Lastly, to ensure objective and impartial oversight, they recommended development of local expertise that is independent of technology developers and sponsors. The CSOs’ perspectives were diverse but broadly aligned with the precautionary principle, calling for preventive action amid uncertainty, clear accountability, and the pursuit of safer alternatives. Although many expressed serious reservations about gene drive mosquitoes, there was a shared recognition that research on the technology is necessary, provided it is conducted under controlled, transparent, and auditable conditions. Overall, these exploratory discussions underscored the need for: (i) balanced dialogue between advocates and skeptics, (ii) robust ethical and regulatory frameworks covering the full life cycle of the technology, (iii) sustained community and stakeholder engagement from the early stages of research and development, (iv) enhancements of in-country capacity, and (v) national sovereignty in decision-making regarding GDMMs. Demonstrating and effectively communicating these elements will be as critical as ensuring their existence.
Florida releases millions of genetically modified mosquitoes from Oxitec in the Florida Keys to try to reduce dengue and Zika by up to 95%, in a real-world experiment that divides residents and ushers in a new era of ecosystem editing.
35351Carla Teles, Click Petróleo e Gás, 2026-01-10 09:57:25.
In a quiet Florida neighborhood, things began with something that seemed mundane. Gray boxes started appearing in backyards and along the edges of mangrove swamps, accompanied by a simple instruction: fill with water and leave. Nobody saw anything special about them, just discreet containers scattered around the neighborhood. What almost nobody realized was that those boxes were capsules for a global experiment: from inside them would emerge millions of mosquitoes. Created in a laboratory, carrying a genetic code designed to attack their own species. In the following months, these boxes became the starting point for waves of millions of mosquitoes A laboratory experiment over the Florida Keys. For some residents, it looked like the beginning of an apocalyptic movie. For others, it was a desperate gamble to contain dengue and Zika outbreaks that had been approaching year after year. And behind it all was Oxitec, a British biotechnology company that transformed a common mosquito into a small flying genetic saboteur.
Monitoring the Capacity of Microsporidia MB Transgenerational Spread in Anopheles arabiensis Populations
35317Boanyah, G. Y., Koekemoer, L. L., Herren, J. K., & Bukhari, T., Insects, 16. 2026-01-05 11:06:39.
Microsporidia MB is a natural symbiont of Anopheles arabiensis Patton, 1905 that blocks Plasmodium transmission without compromising mosquito fitness. Developing this symbiont for malaria control requires a thorough understanding of its transmission dynamics across generations under environmentally relevant conditions. This study aimed to evaluate the transgenerational spread of Microsporidia MB in semi-field settings. From field-collected infected females (G0), several independent replicates of Microsporidia MB-infected An. arabiensis were established and maintained under semi-field conditions for six generations (F1–F6). All the mosquitoes were screened for Microsporidia MB prevalence and infection intensity using qPCR after death. Temperature and humidity and wing size were recorded. Two replicates sustained through F6. Microsporidia MB prevalence and intensity increased from F1 to F3–F4 before declining. A weak positive correlation was observed between prevalence and temperature, but not humidity. Female mosquitoes exhibited higher infection intensities. Female wing size varied across generations, while male size remained consistent. This first study on Microsporidia MB transgenerational transmission under semi-field conditions revealed a pattern of initial increase followed by decline in prevalence and intensity. The stability of male size supports the potential use of infected males in release programs. These findings underscore additional investigations into environmental drivers for mosquito symbiont prevalence.
Genetic Biocontrol Strategy Considerations for Mosquito Control in the Pacific Island Countries and Territories
35315Adam E. Vorsino, Tim Harvey-Samuel, Limb K. Hapairai, et al., Current Opinion in Insect Science, 2026-01-05 10:49:54.
Mosquito-borne diseases pose an existential threat to the health, economies, and unique ecosystems of Pacific Island Countries and Territories (PICTs). The remoteness of these islands, combined with the presence of highly competent mosquito vectors, complicates disease surveillance and vector control efforts. In response, the PICTs have become a focal point for the development and application of Genetic BioControl (GBC) technologies designed to break vector-borne disease transmission cycles. However, the application of GBC tools in this region warrants careful consideration of its unique history, including a legacy of colonialism, and challenges associated with logistic hurdles. Through meaningful community engagement and authentic collaborations, drawing from local knowledge, and building local capacity, the sustainable, efficient and effective deployment of GBC tools may be achieved.
A target product profile for a rapid diagnostic test to monitor mosquito gene drive presence and frequency
35345Prateek Verma, Sebald Verkuijl, Calvin K. Yee, et al., bioRxiv, 2025-12-18 10:23:36.
Malaria remains a major global health challenge, with over 263 million cases and nearly 600,000 deaths reported in 2023, the majority in sub-Saharan Africa. While conventional interventions such as insecticide-treated nets, indoor residual spraying and antimalarial drugs have reduced transmission, progress has stalled due to the limitations of these interventions and the emergence of resistance. Gene drive-modified mosquitoes represent a promising, potentially transformative vector control strategy, capable of spreading malaria-refractory traits or suppressing mosquito populations. Successful field deployment will depend upon monitoring systems to track the presence and frequency of gene drive constructs as they spread and persist. Current molecular surveillance techniques, though effective, are resource-intensive and reliant on laboratory infrastructure and technical competencies. Here, we make the case for a near-universal and low-cost rapid diagnostic test (RDT) designed to detect gene drive mosquitoes in the field, to complement existing surveillance infrastructure. Two use cases are outlined: i) to detect the presence of the drive construct in a new population, and ii) to provide an estimate of drive frequency prior to more accurate laboratory-based measurements. We provide a target product profile for the RDT outlining minimally essential and ideal characteristics, including test procedures, sensitivity, specificity, usability by a range of stakeholders in field settings, and compatibility with pooled testing of mosquito samples. An RDT for gene drive construct detection would support community access and participation in monitoring, enhance regulatory oversight, and promote transparency in field trials, thereby facilitating responsible deployment of gene drive-based malaria interventions.
Rethinking the future of mosquito control
35341Kabirul Bashar, Dr Zonaed Siddiki. Dr Zonaed Siddiki, et al., Dhaka Tribune, 2025-12-17 11:37:26.
Bangladesh is once again in the grip of a severe dengue and chikungunya crisis in 2025. Hospitals are overwhelmed, fever wards are full, and doctors are working tirelessly. Families live in fear of mosquito bites, while daily news reports chronicle rising infections and deaths. As of December 16, 2025, the Directorate General of Health Services (DGHS) has reported more than 100,000 confirmed dengue cases and 409 deaths. However, this figure represents only the tip of the iceberg, as it reflects data solely from hospitalized patients, specifically from 77 hospitals in Dhaka and reports from 64 civil surgeon offices. A substantial number of dengue patients are receiving treatment at home or in various small and large hospitals and clinics that are not included in the official count. This underscores the overwhelming pressure on the country’s health system. At the same time, the Institute of Epidemiology, Disease Control and Research (IEDCR) has recorded a resurgence of chikungunya, reporting 337 suspected cases, 153 of which were laboratory-confirmed in Dhaka between January and May 2025. Researchers estimate that the true number of chikungunya infections this year may be close to one hundred thousand. As chikungunya testing is available only in a limited number of major hospitals in Dhaka, many cases remain undiagnosed and unreported.
Spot the males: New gene-editing method could transform mosquito control
35339Robert Egan, Phys.org, 2025-12-17 11:22:04.
Researchers have developed a new "color-coded" genetic method that makes it easy to distinguish male and female mosquitoes. This innovation can help solve a major bottleneck in mosquito control strategies that rely on releasing only sterile males. The approach uses gene editing to produce dark males and pale females, offering a practical and safer alternative to current sex-separation techniques. A new study led by Doron Zaada and Prof. Philippos Papathanos from the Department of Entomology at Hebrew University, introduces a powerful genetic approach for separating male and female mosquitoes, an essential step for large-scale mosquito control programs aimed at reducing the spread of infectious diseases such as Dengue, Zika, and Chikungunya. Mosquito control strategies based on the mass release of males rely on the complete removal of females, which bite and transmit disease. Existing separation methods, largely based on size differences at the pupal stage, are labor-intensive, difficult to scale, and prone to letting biting females slip through. This new study presents a genetically engineered "Genetic Sexing Strain" (GSS) of the Asian tiger mosquito (Aedes albopictus) that allows sexes to be sorted automatically based on visible pigmentation.
Genetic trick to make mosquitoes malaria resistant passes key test
35307Michael Le Page, New Scientist, 2025-12-10 17:06:06.
A genetic technology known as a gene drive could help prevent malaria by spreading genes in wild mosquitoes that stop them transmitting the parasite. Tests in a lab in Tanzania have now confirmed that one potential gene drive should achieve this if it were released in the country. “It would be a game-changing technology, that’s for sure,” says George Christophides at Imperial College London. A specific piece of DNA in the genome of an animal is normally passed on to only half its offspring, because a parent’s DNA is divided in half among egg or sperm. Gene drives increase this proportion, meaning a bit of DNA can spread rapidly through a population even if it provides no evolutionary benefit. There are many natural gene drives that work via all kinds of mechanisms – perhaps even in some human populations – and in 2013, biologists developed artificial gene drives using CRISPR gene-editing technology, which works by copying pieces of DNA from one chromosome to another. The idea is to use these drives to spread bits of DNA that block malaria transmission – but which bits? Christophides reported in 2022 that the development of malaria parasites inside mosquitoes can be greatly reduced by two tiny proteins, one derived from honeybees and the other from the African clawed frog.
This scientist is breeding billions of mosquitoes to fight disease in Brazil
35301Mariana Lenharo, Nature, 2025-12-08 17:09:18.
nside a massive factory in the industrial district of Curitiba, Brazil, millions of Aedes aegypti mosquitoes are breeding in a climate-controlled room filled with mesh cages. Every week, the facility produces more than 80 million mosquito eggs. At the heart of this effort is Luciano Moreira, a soft-spoken agricultural engineer and entomologist, who opened the factory in July as part of an effort to fight mosquito-borne illnesses in the country. At the Curitiba facility, mosquitoes are infected with a bacterium called Wolbachia, which curbs the transmission of harmful human pathogens. Their offspring are being released in Brazilian cities to help to control dengue, a deadly viral disease transmitted mainly by A. aegypti. Until recently, Wolbachia-carrying mosquitoes were released only as part of small-scale research projects. The new factory marks a shift towards nationwide adoption of the method after Brazil’s federal government recognized it as an official public-health measure to combat dengue and other mosquito-borne diseases. People credit Moreira for making the case. “He has succeeded not only in carrying out the academic work, running experiments to demonstrate the model’s effectiveness, but also in convincing political decision-makers to implement the technology,” says Pedro Lagerblad de Oliveira, a molecular entomologist at Brazil’s Federal University of Rio de Janeiro. “This is a skill that not all scientists have.”
Integrating mosquito genomics into simulation modeling: Opportunities for better-informed biocontrol
35282Gordana Rašić, John M. Marshall, Current Opinion in Insect Science, 2025-11-03 11:25:51.
Mosquito-borne diseases remain a major global health burden, and novel biocontrol tools are quickly advancing from the laboratory to the field. Mathematical models play a central role in evaluating these interventions, yet their predictive accuracy depends on robust parameterization. Population genomics presents a powerful opportunity to address this challenge. Here, we review progress at the interface between mosquito genomics and biocontrol modeling, highlighting how genomic data have informed our understanding of mosquito population structure, standing genetic variation at gene drive target sites, and sources of resurgence for suppressed populations. We also discuss frontiers, including new approaches to quantifying gene flow, mating behaviors, and inbreeding depression, all of which shape intervention outcomes. By tapping this potential to better quantify our understanding of mosquito ecology, modelers can develop context-specific models with better predictive accuracy, supporting efficacy and risk assessment, design of field trials and interventions, and promotion of regulation and public trust.
Highlight: Self-limiting gene drive suppresses malaria mosquitoes
35263Gorm Palmgren, CRISPR Medicine News, 2025-11-02 17:22:29.
Malaria claimed over 600,000 lives in 2022, with Anopheles gambiae serving as one of the most efficient vectors in sub-Saharan Africa, where approximately 96% of malaria deaths occur. The emergence of insecticide resistance threatens progress in disease control, prompting the development of genetic strategies to address it. CRISPR-homing gene drives have emerged as the most studied self-sustaining approaches, whilst various self-limiting methods that require repeated releases continue to be explored. The research team developed a system, termed Male-Drive Female-Sterile (MDFS), that exploits CRISPR-Cas9 to simultaneously perform two distinct functions (see Figure 1). The genetic construct contains an eCFP fluorescent marker, a Cas9 endonuclease under the control of the germline vasa2 promoter, and a guide RNA targeting the female-specific exon 5 of the doublesex gene. The construct was integrated into the doublesex locus at the intron 4–exon 5 boundary using recombinase-mediated cassette exchange.
Intermittent releases: a modelling approach for sterile insect technique in mosquito control
35255Bhattacharyya, J., Banerjee, M. & Banerjee, S, Journal of Mathematical Biology, 91. 2025-10-27 10:49:16.
An unconventional and environmentally friendly mosquito management approach offers a sustainable solution that protects both the environment and human health. One such method is the Sterile Insect Technique (SIT), which holds promise as a mosquito control strategy by releasing sterilized male mosquitoes into the wild-type (WT) mosquito population. Since the success of SIT depends on the strategic planning of sterile mosquito releases, this paper examines a stage-structured model for mosquito populations with a density-dependent threshold for sterile male mosquito release, where releases occur only when the ratio of WT to sterile mosquito populations exceeds a critical threshold. Using intermittent releases, the proposed SIT model is designed to optimally align the release of sterile male mosquitoes with WT and sterile mosquito population densities, maintaining WT mosquito suppression at a predefined threshold and offering a more effective alternative to continuous release strategies. We employ Filippov’s modelling approach to investigate how intermittent releases, represented by piecewise-smooth functions, affect the dynamics of the system, particularly when mosquito populations exceed the predefined threshold. To explore the dynamical complexities, we employ Filippov’s convex method by defining the vector field in the discontinuous region as convex combinations of adjacent fields, allowing for the analysis of sliding motion and the identification of discontinuity-induced bifurcations through differential inclusions. Our findings identify the minimum release rate of sterile mosquitoes required to achieve the desired suppression level, highlighting the need to increase this rate due to increased WT mosquito immigration, reduced survival and mating fitness of sterile mosquitoes, and limitations in mosquito surveillance accuracy.
Requirements for designing cluster randomised control trials to detect suppression of malaria vector population densities
35239Hancock, P.A., Hui, TY.J., Epopa, P.S. et al., BMC Biology, 23. 2025-10-15 08:17:09.
Novel interventions for mosquito-borne disease control which release modified mosquitoes that are sterilised or genetically modified to cause offspring inviability are progressing towards field applications. Cluster randomised control trials (CRCTs) could provide robust assessment of intervention efficacy in suppressing mosquito populations in field environments, but guidance on designing CRCTs to detect mosquito suppression impacts is limited. We developed statistical models to simulate CRCTs, informed by a 5-year time series measuring densities of malaria vector species from the Anopheles gambiae complex in four villages in western Burkina Faso. We estimated requirements for parallel and step wedge designs, varying the targeted vector species, the suppression effect and the monitoring regime. For a suppression effect of 50%, 21–22 clusters were required to detect suppression with 90% power when all An. gambiae complex species were targeted, while 24–26 clusters were required when only An. coluzzii was targeted and 60–66 clusters were required when only An. gambiae was targeted. For stronger suppression effects, required trial sizes depended less on target species, with 9–10 clusters being sufficient to detect a 90% suppression effect. We investigated how reducing sampling effort, by sampling fewer houses and restricting sampling to rainy season months, affected statistical power. Our results provide empirically based guidance for designing CRCTs to evaluate interventions aiming to suppress malaria vector populations.
Bacteria-mediated dsRNA delivery for mosquito-borne virus control
35219Mine Altinli, Sean P. Leonard, Alain Kohl, et al., Trends in Parasitology, 41:880-893. 2025-10-05 14:37:07.
Mosquito-borne viruses represent an increasing global public health threat, exacerbated by urbanisation and climate change, thus making effective mosquito control essential. RNA interference (RNAi), a sequence-specific gene regulation mechanism, can be a flexible vector control tool. RNAi effectors, such as double-stranded RNA (dsRNA), can target mosquito genes or the viruses they carry, disrupting development or suppressing infection. However, current RNAi delivery methods are ineffective. Engineered bacterial symbionts offer a promising alternative for delivery, as they can produce dsRNA directly within mosquitoes. However, bacterial RNAi delivery in mosquitoes remains underexplored. We review emerging genetic tools, insights from RNAi and bacteria–mosquito interactions to outline priorities for realising bacterial RNAi as an efficient and sustainable vector control strategy.
Impact of larval diet on fitness outcomes of Aedes aegypti mosquitoes infected with wAlbB and wMelM
35213Md Yatim, M.F., Ross, P.A., Gu, X. et al., Parasites Vectors, 18. 2025-10-02 15:06:04.
Releases of Wolbachia-infected Aedes aegypti are being used to effectively control diseases caused by arboviruses, such as dengue. A well-balanced larval diet is essential for producing Wolbachia-infected mosquitoes with optimal fitness for release. In this study, four diets with varying protein-to-carbohydrate ratios were tested with three Ae. aegypti lines (carrying the wAlbB, wMelM Wolbachia infections or uninfected) to identify optimal diets for larval rearing on the basis of diet allocations ranging from 0.4 to 3.2 mg/larva/day. The diets were selected on the basis of a review of existing literature and are characterized by progressively increasing protein and decreasing carbohydrate content: diet 1 (Pd) was based on plant-based protein (low protein and high carbohydrate), diet 2 (Kd) was based on animal-based protein (moderate protein and high carbohydrate), diet 3 (Fd) involved Hikari fish food (high protein and moderate carbohydrate), and diet 4 (IAEA) followed a widely used very-high-protein and low-carbohydrate diet developed by the International Atomic Energy Agency (IAEA). The optimal concentration for each diet was determined using a fitness index that incorporated pupation success, fecundity, hatch proportion and development time. The optimal dietary allocations for diets 1–4 were 1.6, 1.2, 1.2 and 0.8 mg/larva/day, respectively, regardless of Wolbachia status. There was a consistent significant positive relationship between female wing length and fecundity in wAlbB (r2 = 0.881), wMelM (r2 = 0.329), and uninfected (r2 = 0.886) mosquitoes. Diet 3 (Fd) at optimal food allocation reduced a fitness cost commonly associated with the wAlbB line compared with the uninfected line when provided at the optimal concentration. The wMelM line showed a persistently low fecundity regardless of diet and concentration. These findings highlight the importance of an appropriate larval diet and dietary allocations in optimizing mosquito fitness for Wolbachia-based vector control programs. Further research into dietary composition, gut microbial interactions and Wolbachia associations could refine larval nutrition strategies, enhancing the effectiveness of mass-rearing for release programs.
Effect of egg irradiation on development and sterility of wild-type and Wolbachia trans-infected Aedes aegypti mosquito vectors
35170Kittayapong P, Ninphanomchai S, Thayanukul P, Limohpasmanee W, PLoS One, 20. 2025-09-26 13:56:46.
Sterile Insect Technique (SIT), Incompatible Insect Technique (IIT) or a combination of the two has become alternative promising vector control approaches. In order to apply these approaches, the targeted mosquitoes need to be sterilized and released. So far, the irradiation of mosquitoes has been conducted at the pupae or adult stages. In this study, we investigated the possibility of applying X-ray irradiation at the egg stage and also assessed the effect on the development and sterility of both wild-type and Wolbachia trans-infected Aedes aegypti mosquito vectors. The eggs of both wild-type and Wolbachia trans-infected lines were irradiated using X-ray at the doses of 1, 3, 5 and 7 Gy. Development of immature stages was observed. For wild-type Ae. aegypti, X-ray irradiation at the doses from 3 Gy decreased the development of the first-instar larvae and increased the development of the third-instar larvae but there was no effect on pupae. For Wolbachia trans-infected ones, a irradiation dose as low as 1 Gy could increase the development of the forth-instar larvae while an irradiation dose of 7 Gy induced significantly high mortality to the pupae (p < 0.05). To assess sterility, males and females that emerged from irradiated eggs were mated with the non-irradiated ones. Our results showed that an irradiation dose of 7 Gy significantly caused more than 90% sterility in both wild-type males and females (p < 0.05). However, this irradiation dose could be reduced to 5 Gy to sterilize both males and females infected with Wolbachia. Our findings revealed, for the first time, that applying a low-dose X-ray irradiation at the egg stage could sterilize both wild-type and Wolbachia trans-infected Ae. aegypti when they become adults. Egg irradiation could make the implementation of SIT, IIT or combined SIT/IIT for vector control much more feasible as the sterile eggs are easier to distribute and operate when compared to other developmental stages of mosquitoes.
How billions of hacked mosquitoes and a vaccine could beat the deadly dengue virus
35143Lucila Pinto, Nature, 645:578-580. 2025-09-17 14:21:03.
Last month, a parade of vehicles wound its way through three cities in Brazil, releasing clouds of mosquitoes into the air. The insects all carry a secret weapon — a bacterium called Wolbachia that lowers the odds that the mosquitoes can transmit the dreaded dengue virus to humans. These infected mosquitoes are the latest weapon in Brazil’s fight against dengue, which infects millions of people in the country each year and can be fatal. A biofactory that opened in the town of Curitiba in July can produce 100 million mosquito eggs per week — making it the largest such facility in the world. The company that runs it, Wolbito do Brasil, aims to protect about 14 million Brazilians per year through its Wolbachia-infected mosquitoes. That will come as welcome news for the Brazilian health officials battling the rapidly growing threat of dengue. In 2024, the country experienced its worst outbreak yet: with 6.6 million probable cases and more than 6,300 related deaths. This year’s outbreak, although less severe, is also one of the highest on record, with 1.6 million probable cases so far (see ‘Dangerous outbreaks’). And the problem is spreading. Argentina, Colombia and Peru also experienced record-breaking outbreaks in 2024 and have seen a sustained increase in cases in recent years. Across Latin America and the Caribbean, deaths from dengue last year totalled more than 8,400 and the global figure reached more than 12,000 — the highest ever recorded for this disease.
The Urgent Need for More Research on Wolbachia-Based Mosquito Interventions in Public Health
35133Osvaldo Marinotti, Acta Tropica, 2025-09-15 15:36:56.
The release of Wolbachia pipientis-infected Aedes aegypti mosquitoes has emerged as a novel strategy to reduce the transmission of arboviruses such as dengue, chikungunya, and Zika. Wolbachia-based approaches to dengue control include population replacement, which reduces vector competence by establishing Wolbachia in wild populations of Aedes aegypti, and population suppression, which lowers mosquito densities through cytoplasmic incompatibility. Field trials of the population replacement strategy, based on wMel Wolbachia-infected mosquitoes, have shown variable success and concerns persist about long-term efficacy, safety and ecological impact. Uncertainties arise from an incomplete understanding of the mechanisms underlying pathogen blocking, possible bacteria and vector strain-specific effects, and the influence of environmental, host, and viral factors on the success of such a strategy. Moreover, some Wolbachia strains may enhance mosquito susceptibility to certain pathogens. Additionally, large-scale deployment raises the possibility of biodiversity disruption and the emergence of viral resistance. Given these unresolved concerns, it is premature and potentially irresponsible to expand the program to new areas without first rigorously assessing its safety, efficacy and sustainability.
Nature goes inside the world’s largest ‘mosquito factory’ — here’s the buzz
35120Adam Levy & Mariana Lenharo, Nature, 2025-09-08 08:31:27.
Raising mosquitoes to tackle disease might sound like an odd concept, but that’s what a facility in Brazil is aiming to do. Millions of mosquitoes are produced there every week, but these insects carry harmless Wolbachia bacteria that curbs their ability to spread deadly human viruses. Nature reporter Mariana Lenharo visited the facility and told us all about her experience in this Podcast Extra.
This is the world’s largest ‘mosquito factory’: its goal is to stop dengue
35109Mariana Lenharo, Nature, 2025-09-03 09:20:02.
When biologist Antonio Brandão tells people that he works at a mosquito factory, they are often baffled. Why would you make more mosquitoes?, he recalls people asking. “We have enough of them.” But once he explains that the laboratory-raised insects can help to stop the spread of dengue — which strikes hundreds of thousands in Brazil each year with fever, headache and bone pain — they come around. Brandão is the production manager, not at just any mosquito factory, but at the world’s largest, located in the southern Brazilian city of Curitiba. Launched in July, the facility is expected to produce 100 million eggs a week from the mosquito Aedes aegypti. However, unlike wild A. aegypti, the main transmitter of dengue virus, those churned out by the factory carry a harmless Wolbachia bacterium that curbs the insects’ ability to spread viruses including dengue and Zika. The idea is to release the modified mosquitoes, which researchers call wolbitos, into cities in Brazil, where they will mate with their wild counterparts and the females will pass the bacterium on to their offspring, gradually converting the local population. The wolbito strategy, which is being spearheaded by the non-profit World Mosquito Program (WMP), has already shown success in Colombia, Indonesia and at home: in the Brazilian city of Niterói in the southeast, dengue cases dropped by 69% in areas where Wolbachia-carrying mosquitoes were released, compared with areas where they weren’t1. Brazil’s federal government has adopted the approach to fight dengue infections — which surged to a record 6.5 million confirmed cases in the country last year — alongside other preventive measures such as vaccines.
Governance Landscape of Gene Drive for Malaria
35069GeneConvene Global Collaborative, 2025-08-28 10:24:11.
This infographic presents a hypothetical example of how real governance mechanisms could work to make decisions about gene drive field trials.
Emerging challenges for mosquito-borne disease control and the promise of symbiont-based transmission-blocking strategies
35064Gao H, Hu W, Cui C, Wang Y, Zheng Y, Jacobs-Lorena M, et al., PLoS Pathog, 21. 2025-08-26 17:16:49.
Mosquitoes serve as vectors for a variety of pathogens that cause life-threatening diseases, such as malaria, dengue, Zika, and yellow fever. With the rise of antimalarial drug resistance and a lack of therapeutics or prophylactics for dengue and Zika, current disease control strategies rely heavily on mosquito population management. However, the effectiveness of conventional approaches is increasingly compromised, highlighting an urgent need for innovative tools to combat mosquito-borne diseases. One promising strategy for blocking the transmission of these diseases is to populate mosquitoes with anti-pathogen gut symbionts. Here, we discuss the major challenges facing current mosquito-borne disease control efforts and explore how mosquito gut microbiota-based control strategies may address them. We highlight recent advances that may accelerate field applications and offer perspectives on future directions and the translational potential of symbiont-based strategies for mitigating mosquito-borne disease transmission.
How biotech helps Florida Keys prevent mosquito-borne diseases
35029Janine Stanwood, Local 10, 2025-08-17 19:49:34.
Biologists with the Florida Keys Mosquito Control District (FKMCD) are releasing lab-modified mosquitoes twice a week in the Middle Keys. It’s part of a pilot program to reduce the population and help stop people from getting bitten. “They’re male Aedes aegypti,” said Dr. Larry Hribar, FKMCD Director of Research. “They’re infected with a mosquito parasite that’s in the genus Wolbachia.” There are dozens of species of blood suckers in South Florida, including the nuisance salt marsh mosquito found in mangroves and in the Everglades. But it’s the Aedes aegypti that carries diseases like Zika and dengue. “That’s the one that vector the diseases we worry about,” said FKMCD spokesperson Chad Huff. The males, shipped from a company called MosquitoMate, have been infected with the Wolbachia bacteria before mating with females after being released. “They’ll find a local female, they’ll mate, but the eggs she produces are not going to be viable,” Hribar said. According to the Centers for Disease Control, the lab-infected mosquitoes can’t make people or animals sick.
Spatiotemporal complexity in interacting wild and sterile mosquito populations
35005Mandal, G., Guin, L.N. & Chakravarty, S., Nonlinear Dyn, 2025-08-04 08:39:42.
In the present exploration, a mosquito population model is investigated that incorporates a non-linear, saturated release rate for sterile mosquitoes. The model framework leverages a reaction-diffusion system to generate spatiotemporal patterns. A thorough theoretical analysis is conducted to explore the model’s feasible equilibria, focusing on the phenomenon of bistability. Subsequently, the stability, instability, and potential bifurcation scenarios are examined rigorously. Each identified bifurcation is then utilized to elucidate the complex dynamical behaviour of the system. The entire parameter space is systematically partitioned by simultaneously varying two key parameters. This partitioned space can then be further analyzed in conjunction with one and two-parameter bifurcation diagrams. This approach facilitates a deeper understanding of the system’s dynamics within each identified region. In two dimensions (2D), the evolution of diffusion-driven pattern formation is presented for various scenarios, including spots, stripes, labyrinthine structures, combinations of stripes and holes, and hole replication. These spatial patterns are demonstrated to be influenced by critical system factors associated with the concept of Turing space. Sensitivity analysis reveals that the number of wild offspring produced per mating event is the most sensitive parameter within the model. Moreover, the present investigation admits dynamical codimension one and two bifurcations concerning the induced most sensitive parameter. The theoretical findings are consistently validated and corroborated by numerical simulations, which are further employed to evaluate the biological implications of the theoretical results.
Thousands of mosquitoes are being dropped by drone over islands in Hawaii. Here’s why
34999Nell Lewis, CNN, 2025-07-31 15:47:51.
In June, dozens of biodegradable pods fell from the sky over the forests of Hawaii. Each one, delivered by drone, contained about 1,000 mosquitoes. These weren’t just any mosquitoes — they were non-biting, lab-reared male mosquitoes carrying a common bacterium that results in eggs that don’t hatch when the males mate with wild females. The hope is that they will help to control the archipelago’s invasive mosquito population, which is decimating native bird populations, such as rare Hawaiian honeycreepers. The birds, which are key pollinators and seed dispersers and also play a central role in Hawaiian culture, are in dire straits. There were once more than 50 known species of honeycreepers in Hawaii, but today there are only 17 left, most of which are endangered. Last year, the ‘akikiki, a small gray bird, went functionally extinct in the wild, and less than 100 of the yellow-green ʻakekeʻe are estimated to remain. Development and deforestation have had an impact, but according to Dr. Chris Farmer, Hawaii program director for the American Bird Conservancy (ABC), the “existential threat” is avian malaria, which is spread by mosquitoes.
Knowledge, attitude, and practice (KAP), and acceptance and willingness to pay (WTP) for mosquito-borne diseases control through sterile mosquito release in Bangkok, Thailand
34991Kittayapong P, Ninphanomchai S, Jalichandra N, Sringernyuang L, Sherer P, Meemon N, PLoS Negl Trop Dis, 19. 2025-07-30 11:03:04.
A questionnaire survey was conducted in seven communities in Bangkok, Thailand to obtain baseline information on knowledge, attitudes and practices (KAP) related to mosquito-borne diseases, i.e., dengue, chikungunya and Zika, including mosquito vectors and how to control them. The questionnaire also asked about the acceptance and willingness to pay (WTP) for sterile mosquitoes used in controlling mosquito populations. Our results showed that, from a total of 400 sampling households, about 85% of participants were familiar with dengue and its mosquito vectors, as well as their prevention and control. Furthermore, participants with lower ages and higher incomes had more knowledge on mosquito vectors (p < 0.05). Even though the majority of participants did not have any knowledge on sterile mosquito release, they showed a positive perception about it. However, more than half of them were not willing to pay for sterile mosquitoes, since they would like to receive them as public support from the government. If they were to pay, the cost that they could afford was 1–2 THB (~US$ 0.03- 0.06) per sterile mosquito. These findings should be useful for public health authorities when planning to apply the sterile mosquito release as an alternative mosquito control approach in Bangkok, Thailand.
Controversial ‘gene-drive’ strategy could make mosquitoes hostile to malaria parasites
34977Mitch Leslie, Science, 2025-07-24 09:37:48.
To fight malaria and the mosquitoes that spread it, people have drained swamps, showered their homes with insecticides, slathered themselves in noxious repellents, hidden under netting at night, and invented the gin and tonic—as a palatable way to take the bitter antimalarial quinine. Now, researchers report in Nature that they have borrowed a weapon from the mosquitoes themselves. The team genetically engineered mosquitoes to be resistant to parasites that cause malaria by inserting a version of a gene naturally found in some of the insects. They also enlisted a genetic trick known as gene drive to speed the gene variant's spread through mosquito populations in the lab. The strategy is not ready for field testing, researchers caution. But the experiments "are elegantly designed and sound, really showing great proof of principle for driving natural variants of mosquito genes into a population," says functional geneticist Tony Nolan of the Liverpool School of Tropical Medicine, who wasn't connected to the study.
A genetic tweak could prevent mosquitoes from transmitting malaria
34987Jonathan Lambert, NPR, 2025-07-23 10:40:28.
Each year, 263 million people get malaria. But from the parasite's perspective, infecting humans is harder than you might think, and requires completing an epic journey within the tiny body of a mosquito. First, the mosquito must suck the blood of an individual infected with malaria — bringing the Plasmodium parasite into the insect's gut. Then the parasite must travel to the critter's salivary glands, where it's poised to be injected into the mosquito's next victim via a bite. Now a team of researchers have found a way to interrupt this crucial journey. By using gene editing to make a tiny tweak to the mosquito's genome — one that changes just a single amino acid — parasites were largely prevented from reaching their final destination. The change effectively rendered laboratory mosquitoes highly resistant to spreading malaria, researchers report Wednesday in Nature. "The idea that you could change just one amino acid and not have the parasite transmitted is a pretty big deal," says Fred Gould, an entomologist at North Carolina State University who wasn't involved in the study. "It's really exciting." That tiny tweak could be spread through a whole mosquito population using a gene drive, a genetic technology that breaks the normal 50-50 rules of inheritance. Gene drives are sequences of DNA that can be inserted into the genome of an individual and cause a specific mutation or gene to be passed on to virtually all offspring, instead of just 50%.
Genetic tweak in mosquitoes blocks malaria transmission without affecting insect health
34978University of California - San Diego, Phys.org, 2025-07-23 09:38:04.
Mosquitoes kill more people each year than any other animal. In 2023, the blood-sucking insects infected a reported 263 million people with malaria, leading to nearly 600,000 deaths, 80% of which were children. Recent efforts to block the transmission of malaria have been stalled because mosquitoes have adapted resistance to insecticides and the parasites within mosquitoes that cause malaria have become resistant to drugs. These setbacks have been amplified by the COVID-19 pandemic, which impeded ongoing anti-malarial efforts. Now, researchers at the University of California San Diego, Johns Hopkins University, UC Berkeley and the University of São Paulo have developed a new method that genetically blocks mosquitoes from transmitting malaria. Their work appears in Nature. Biologists Zhiqian Li and Ethan Bier from UC San Diego, along with Yuemei Dong and George Dimopoulos from Johns Hopkins University, created a CRISPR-based gene-editing system that changes a single molecule within mosquitoes, a minuscule but effective change that stops the malaria-parasite transmission process. Genetically altered mosquitoes are still able to bite those with malaria and acquire parasites from their blood, but the parasites can no longer be spread to other people. The new system is designed to genetically spread the malaria resistance trait until entire populations of the insects no longer transfer the disease-causing parasites. "Replacing a single amino acid in mosquitoes with another naturally occurring variant that prevents them from being infected with malarial parasites—and spreading that beneficial trait throughout a mosquito population—is a game-changer," said Bier, a professor in the UC San Diego Department of Cell and Developmental Biology (School of Biological Sciences). "It's hard to believe that this one tiny change has such a dramatic effect."
A male-drive female-sterile system for the self-limited control of the malaria mosquito Anopheles gambiae
34945Anna Strampelli, Katie Willis, Hannah Robyn Gulliford, et al., bioRxiv, 2025-06-24 10:02:54.
The use of insecticides and antimalarial drugs has been crucial in reducing the mortality and morbidity associated with malaria. However, since 2015, several challenges, including the development of resistance to these insecticides and treatments and changes in mosquito behaviour, have hindered the progress in fighting the disease. As a result, there is a pressing need for new tools to control malaria, including the potential use of genetically modified mosquitoes (GMMs) in the field. Various genetic strategies for vector control are currently being explored, ranging from self-sustaining GMMs with unrestricted geographic and temporal spread to self-limiting alternatives. Here, we propose a self-limiting gene drive strategy called Male Drive Female Sterile (MDFS) targeting Anopheles gambiae, a major malaria vector. The MDFS genetic construct causes dominant sterility in females, while transgenic males remain fertile, allowing them to transmit the female sterility trait at super-Mendelian rates. Laboratory studies have shown that repeated releases of MDFS can lead to the elimination of caged mosquito populations. Based on these findings, modelling suggests that MDFS could be a highly effective and self-limiting strategy for suppressing wild malaria mosquito populations.
Importation of the non gene drive male bias mosquito to Uganda
34926Target Malaria, YouTube, 2025-06-23 14:55:08.
This video documents the importation of non gene drive male bias mosquitoes by Target Malaria’s team in Uganda. The video follows the journey from Entebbe Airport to the Arthropod Containment Level 2 (ACL2) insectary at the Uganda Virus Research Institute, highlighting key moments such as interviews with project staff and stakeholders—including regulatory officials and members of the community consultative group. It also captures the process of unpacking the eggs from the secure packaging and transferring them to the larval trays. Produced in both English and Luganda, this video is designed for project stakeholders, supporting presentations and other communication efforts to keep communities and partners informed about the project’s activities in Uganda.
Create legal path for gene drive mosquitoes, experts say
34919Samwel Doe Ouma, The Star, 2025-06-23 10:42:22.
As Africa continues to shoulder the global burden of malaria, scientists and policy experts say gene drive technology could offer a groundbreaking solution. But without clear regulatory frameworks and strong community engagement, its deployment could be delayed, risking further loss of life and economic productivity. During the Evidence for Development (EVI4DEV) Conference in Nairobi, hosted by the African Union Development Agency (AUDA-NEPAD), the Science for Africa Foundation (SFA), and the African Institute for Development Policy (AFIDEP), experts called for urgent policy harmonisation and public dialogue to enable the safe rollout of gene drive technology. “Malaria is an African problem, we need to find our own tools to address malaria problems,” said Dr Barbara Glover from AUDA-NEPAD, South Africa. “Africa should be able to innovate new technologies and solutions for African problems.” Gene drive technology targets malaria-transmitting mosquitoes by altering their genetic makeup, specifically the Anopheles gambiae species, to pass on traits such as infertility, reducing mosquito populations over time. The approach, being developed under the Target Malaria consortium, has shown promise in laboratory settings but has not yet been tested in the field. “Gene drives systems promote the biased inheritance of specific genes from one generation to the next,” explained Dr Wiltshire Johnson of AUDA-NEPAD. “Gene drive is deployed when a causal pathway initiated by release of a gene drive system in target mosquito vector species, leading to its transmission to subsequent generations, its increase in frequency and spread in target mosquito populations, its simultaneous propagation of a linked genetic trait aimed at reducing vectorial capacity of plasmodium and reduced vectorial capacity for parasites in target mosquito populations resulting in decreased malaria incidence and prevalence.” Johnson emphasised the urgency of adopting innovative tools amid increasing resistance to existing malaria interventions such as insecticides and drug treatments. “Malaria still kills 600,000 people, causes reduction of 25 percent GDP in Africa countries,” he said. “Even with existing traditional Malaria control tools starting to fail or are showing signs of failure... the deployment and use of gene drive technology will help in solving the malaria problem.”
Mozzie: a computationally efficient simulator for the spatio-temporal modelling of mosquitoes
34916Wilkins et al., Journal of Open Source Software, 10. 2025-06-16 13:04:27.
Mozzie enables simulation of the lifecycle and spatial spread of mosquitoes. Mozzie can be used to assess risks associated with disease-control strategies at local, regional or continental scales. Most particularly, strategies involving genetic alterations of mosquitoes to eliminate malaria, are of prime interest. More technically, Mozzie simulates a population-dynamics model that uses differential equations or delay differential equations (Bohner et al., 2018; El-Hachem & Beeton, 2024) to describe the spread and persistence of mosquitoes that may be genetically altered. Genetic alterations are flexibly modelled: these can involve any number of alleles; Mendelian or non-Mendelian inheritance, including gene drives; they can be self-limiting or self-sustaining; and can include the emergence of resistant allelles. The model allows simulation of 𝑁 mosquito species. It incorporates mate-choice, hybridisation and intra-specific competition that occur within complexes of mosquito species (Beeton et al., 2020). This fills a gap that currently exists among similar models, allowing researchers to assess potential transfer of the genetic alterations between (sub-)species. Mozzie supports spatial and temporal variations in lifecyle parameters, and local diffusion andwind-assisted, long range, advection. For example, wind patterns and the capacity of the landscape to support mosquitoes can vary spatially and temporally, reflecting daily variations, seasonality, and local conditions. Conversely, Mozzie does not contain human agents, nor does it consider the effect of genetic control strategies on the prevalence of pathogens such as the malaria parasite, among human or animal populations. Mozzie has been used by the authors to simulate the spread across sub-Saharan Africa of a theoretical, population-modifying, gene drive in Anopheles gambiae s.s. and Anopheles coluzzii (Beeton et al., 2022) (that paper also describes the mathematics of a particular mosquito lifecycle model that is contained in Mozzie). It has also been used to predict the spread of Target Malaria’s Paternal Male Bias construct (Galizi et al., 2014) following a proposed field-release of genetically modified Anopheles coluzzi male mosquitoes in Burkina Faso (Hosack et al., 2023).
Modelling and sensitivity analysis to control dengue through inclusion of genetically modified hybrid mosquitoes
34907Wasim, T., Ismaeel, T., Naseem, A., Abdeljawad, T., & Alqudah, M. A., Mathematical and Computer Modelling of Dynamical Systems, 31. 2025-06-15 18:50:47.
Dengue fever, an ancient yet persistent global health threat transmitted by mosquitoes, remains difficult to control. Recent advances propose genetically modified hybrid mosquitoes as a novel intervention. This study focuses on two primary control strategies: the Sterile Insect Technique (SIT) and genetic sterilization. SIT involves releasing sterile male mosquitoes to reduce populations through unsuccessful mating, while genetic sterilization targets mosquito reproduction or virus transmission capabilities. In our proposed model, modified mosquitoes are included in the susceptible vector compartment, denoted as ℧𝑚. Diagnosis and treatment are modeled with parameters 𝑑1 and 𝑑2. Field and laboratory studies suggest these methods effectively reduce mosquito populations and dengue incidence. A mathematical model is developed to study this strategy’s impact, incorporating the basic reproduction number 𝑅0 and equilibrium analysis. Numerical methods are used to assess system stability and compute sensitivity indices 𝒲ℋ𝜉, ultimately demonstrating the potential for effective dengue control.
Battle of the mosquitoes
34911Adepoju, P, Nature Medicine, 2025-06-11 19:05:47.
The mosquito was frozen in place. Its tiny body, no longer buzzing, lay still on the cold metal surface, caught in a moment of stasis. A few minutes earlier, it had been active, darting around Oxitec’s research facility, a modified version of nature’s most dangerous killer. “We put them on ice because that slows them down”, an Oxitec scientist explained, adjusting the microscope. “It makes our job easier”. This laboratory in Abingdon, England, is where an ambitious mosquito control project is unfolding. The work being done here — modifying Anopheles stephensi mosquitoes to fight malaria—has implications not just for Djibouti, where the genetically modified insects are being released, but for the entire African continent. Outside, it’s a chilly 7 °C, but the lab is surprisingly warm and humid: a digital thermometer plugged in beside the microscope reads 21.1 °C — perfectly mimicking a mosquito’s natural habitat. Large cages fill a section, each holding different generations of modified mosquitoes, bred with a self-limiting gene that ensures that only male offspring survive when they mate with wild females. On one side of the lab, scientists peer into microscopes, searching for a tiny fluorescent marker inside the mosquitoes’ bodies — a glowing signature that confirms the genetic modification was successful. Each mosquito is carefully examined (Fig. 1), its fate decided under the magnifying glass.
Evaluating the performance of three packing methods for long-distance transport of sterile adult Aedes albopictus males
34893Mamai, W., Puggioli, A., Wallner, T. et al., Scientific Reports, 15. 2025-06-06 08:21:38.
This study evaluated the performance of three packing methods for long distance transport of sterile adult Aedes albopictus males, considering the specific effects of pupal vs. adult irradiation and two compaction methods. The results indicated that while transportation significantly impacted the quality of sterile males, all the three packing methods (IAEA V.1.0, IAEA V.2.0, and CAA) tested under simulated transportation durations of 25–48 h resulted in average mortality rates below 12%, with male escape rates ranging between 30 and 50% after a 24-h recovery period. The transported males were able to survive for about 2 days under stress conditions. Additionally, adult irradiation led to higher male survival and escape rates than pupal irradiation, for both before and after transportation. The study also found that stacked cups were more effective as compaction method than the square plastic boxes, despite having a reduced maximum transport capacity. Providing sterile males with 10% sugar for a 24-h recovery period after transportation, also played a role in enhancing escape rate and survival. Although Ae. albopictus prove to be more sensitive to packaging and shipping procedures compared to Aedes aegypti, this study provides valuable insights for developing and improving handling packing and shipping guidelines.
We finally may be able to rid the world of mosquitoes. But should we?
34901Dino Grandoni, Wall Street Journal, 2025-06-03 08:39:56.
They buzz, they bite, and they cause some of the deadliest diseases known to humanity. Mosquitoes are perhaps the planet’s most universally reviled animals. If we could zap them off the face of the Earth, should we? The question is no longer hypothetical. In recent years, scientists have devised powerful genetic tools that may be able to eradicate mosquitoes and other pests once and for all. Now, some doctors and scientists say it is time to take the extraordinary step of unleashing gene editing to suppress mosquitoes and avoid human suffering from malaria, dengue, West Nile virus and other serious diseases. “There are so many lives at stake with malaria that we want to make sure that this technology could be used in the near future,” said Alekos Simoni, a molecular biologist with Target Malaria, a project aiming to target vector mosquitoes in sub-Saharan Africa. Yet the development of this technology also raises a profound ethical question: When, if ever, is it okay to intentionally drive a species out of existence?
Optimizing larval mass-rearing techniques for Aedes mosquitoes: enhancing production and quality for genetic control strategies
34858Wadaka Mamai, Cécile Brengues, Hamidou Maiga, et al, Parasite, 32. 2025-05-26 20:56:36.
The quantity and quality of laboratory-reared insects are pivotal for the success of any sterile male-release program. Optimizing larval mass-rearing methods to enhance both production and quality in Aedes mosquitoes is essential to meet the growing demand from FAO/IAEA Member States for the sterile insect technique (SIT) as a component of area-wide integrated pest management to control or suppress disease vectors. This study was designed to identify the most effective feeding regime and schedule that maximize pupae production with a single tilt/sorting event and to evaluate an alternative larval-rearing unit. The results demonstrated that ingredient particle size, mosquito strain and feeding regime significantly influenced insect production and quality, underscoring the critical need to account for these factors in mass-rearing operations. A daily feeding regime of 0.17, 0.33, 0.67, 0.67 and 0.5 mg per larva was identified as optimal for both species (Ae. aegypti and Ae. albopictus) achieving up to 80 ± 2.5% male pupae recovery rate when sorted 48 h after the onset of pupation. Production outcomes were not compromised with the exclusion of feeding on Days 2 and 3. Furthermore, under the conditions of this study, the Wolbaki rack (Model WBK-P0003-V2) was shown to be sufficient for mass-rearing Aedes mosquitoes. Finally, a 4-day feeding regime was implemented in a field program on Reunion island, yielding similar pupae recovery rates and contamination as the reference regime, a significant step toward improving cost-efficiency and scaling-up the program. These findings provide valuable information for refining standard operating procedures (SOPs) for mass-rearing, thereby enhancing the efficiency and scalability of SIT programs.
Differential elimination of marked sex chromosomes enables production of nontransgenic male mosquitoes in a single strain
34839A. Compton, A. Sharma, M. Hempel, A. Aryan, J.K. Biedler,M.B. Potters, K. Chandrasegaran, C. Vinauger, & Z. Tu, Proceedings of the National Academy of Sciences, 122. 2025-05-12 20:01:30.
Diverse genetic strategies are being pursued to control mosquito-borne infectious diseases. These strategies often rely on the release of nonbiting males to either reduce the target mosquito population or render them resistant to pathogens. Male-only releases are important as any contaminating females can bite and potentially transmit pathogens. Despite significant efforts, it remains a major bottleneck to reliably and efficiently separate males from females, especially when nontransgenic males are preferred. In the yellow fever mosquito Aedes aegypti, sex is determined by a pair of homomorphic sex chromosomes, with the dominant male-determining locus (the M locus) and its counterpart (the m locus) embedded in an M-bearing and an m-bearing chromosome 1, respectively. We utilized both naturally occurring and engineered sex-linked recessive lethal alleles (RLAs) to create sex separation strains for Ae. aegypti on the basis of differential elimination of marked sex chromosomes (DeMark). DeMark strains are self-sustaining and produce nontransgenic males that are readily separated from individuals carrying RLA- and transgene-marked m chromosomes. For example, the marked m chromosome in the heterozygous mother in some strains was only inherited by her female progeny due to RLA-mediated incompatibility with the M-bearing chromosome in the father, producing nontransgenic males and transgenic females, generation after generation. We further explore strategies to conditionally eliminate females that contain marked sex chromosomes. We also discuss DeMark designs that are applicable for efficient sex separation in organisms with well-differentiated X and Y chromosomes, such as the Anopheles mosquitoes.
Mosquito Miracle: Breakthrough Brings Hope for Bangladesh in Dengue Fight
34837Staff Correspondent, Digi Bangla Tech, 2025-05-10 19:42:52.
A major scientific breakthrough is offering new hope for Bangladesh in its battle against dengue. An international team of researchers has successfully developed a strain of Aedes aegypti mosquitoes infected with Wolbachia bacteria, which are capable of adapting to the local environment of Dhaka city. Dubbed as “good mosquitoes,” this innovation opens a new, safe, and biological pathway for controlling the spread of dengue and other mosquito-borne arboviral diseases in the country, according to the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). The research team includes scientists from QIMR Berghofer Medical Research Institute in Australia, the University of Queensland, icddr,b, and the United States Centers for Disease Control and Prevention. The findings were recently published in the journal Nature’s Scientific Reports. According to icddr,b, dengue has emerged as a severe public health threat in Bangladesh. In 2023 alone, a record 321,000 people were infected, with more than 1,700 deaths—making it the deadliest year on record. Rapid urbanization, erratic rainfall, and rising temperatures have contributed to the spread of Aedes mosquitoes, the primary vector of dengue. Simultaneously, the effectiveness of conventional insecticide-based mosquito control methods is declining due to growing resistance among mosquito populations. This has prompted scientists worldwide to seek more sustainable solutions, with the use of "good mosquitoes" being one of the most promising. Researchers explained that Wolbachia was chosen because it prevents Aedes mosquitoes from transmitting dengue, chikungunya, and Zika viruses, without harming humans or the environment. Wolbachia is a naturally occurring bacterium found in butterflies, fruit flies, and some mosquito species, though not in Aedes aegypti. This bacterium cannot infect humans or animals, nor is it transmissible through bites or contact.
Nanobody-mediated targeting of Plasmodium falciparum PfPIMMS43 can block malaria transmission in mosquitoes
34819Ukegbu, C.V., Mohamed, M., Hoermann, A. et al., Communications Biology, 8. 2025-05-04 18:21:46.
The transition from ookinete to oocyst is a critical step in the Plasmodium falciparum lifecycle and an important target for malaria transmission-blocking strategies. PfPIMMS43, a surface protein of P. falciparum ookinetes and sporozoites, is critical for this transition and aids the parasite in evading mosquito immune responses. Previous studies demonstrated that polyclonal PfPIMMS43 antibodies reduced P. falciparum infection in Anopheles mosquitoes. Here, building on these findings, we have developed high-affinity single-domain VHH antibodies (nanobodies) derived from llama heavy-chain-only antibodies. We have shown that these nanobodies bind both recombinant and endogenous PfPIMMS43 produced by P. falciparum ookinetes in the mosquito midgut. Importantly, they significantly reduce infection intensity and prevalence of laboratory and field strains of P. falciparum in An. coluzzii and An. gambiae, respectively. Epitope mapping has revealed that the nanobodies target conserved regions in the second half of PfPIMMS43, with homology modelling confirming epitope accessibility. These findings establish PfPIMMS43 as a promising transmission-blocking target. To enhance malaria control and elimination efforts, we propose an innovative strategy in which genetically modified mosquitoes express PfPIMMS43-specific nanobodies in their midguts and spread this trait in wild mosquito populations via gene drive technology.
Optimization of SgRNA expression with RNA pol III regulatory elements in Anopheles stephensi
34801Gonzalez, E., Anderson, M.A.E., Ang, J.X.D. et al., Scientific Reports, 15. 2025-04-23 11:08:06.
Anopheles stephensi, a major Asian malaria vector, is invading Africa and has been implicated in recent outbreaks of urban malaria. Control of this species is key to eliminating malaria in Africa. Genetic control strategies, and CRISPR/Cas9-based gene drives are emerging as promising species-specific, environmentally friendly, scalable, affordable methods for pest control. To implement these strategies, a key parameter to optimize for high efficiency is the spatiotemporal control of Cas9 and the gRNA. Here, we assessed the ability of four RNA Pol III promoters to bias the inheritance of a gene drive element inserted into the cd gene of An. stephensi. We determined the homing efficiency and examined eye phenotype as a proxy for non-homologous end joining (NHEJ) events in somatic tissue. We found all four promoters to be active, with mean inheritance rates up to 99.8%. We found a strong effect of the Cas9-bearing grandparent (grandparent genotype), likely due to maternally deposited Cas9.
Evolutionary consequences of long-distance dispersal in mosquitoes
34776Thomas L Schmidt, Current Opinion in Insect Science, 68. 2025-04-18 10:25:09.
Long-distance dispersal (LDD) provides a means for mosquitoes to invade new regions and spread adaptive alleles, including those conferring insecticide resistance. Most LDD takes place on human transport vessels and will typically be rarer and more directionally constrained than active flight but can connect populations and regions that are otherwise mutually inaccessible. These features make LDD worthy of specific consideration in mosquito research. This paper reviews recent evolutionary research on LDD and its consequences for mosquito populations and mosquito control. LDD is the main source of mosquito range expansions, and genomic methods can now trace the origins of new invasions to specific towns or cities. Genomic methods can also give a rough indication of the number of invaders, which if very small may lead to the stochastic loss of advantageous alleles during invasion bottlenecks. Once invasions are established, LDD spreads adaptive alleles between populations. Emerging insights into insecticide resistance evolution indicate that LDD has repeatedly spread resistance mutations across global species ranges, but these broad patterns are convoluted by two other evolutionary processes: parallel adaptation at the same gene or gene cluster and polygenic adaptation at different genes in different populations. Together, these processes have produced patterns of similarity and dissimilarity at resistance genes that are decoupled from geographical distance. LDD within cities is less well studied but is important for planning and evaluating local control efforts. Urban investigations of LDD may help identify areas experiencing weaker selection pressures from insecticides and isolated areas to target for control.
Anticipating evolutionary responses of mosquito mating systems to population suppression with mass-reared males
34745Bonsall, M.B., Cator, L.J., Current Opinion in Insect Science, 68. 2025-04-06 19:52:32.
Strategies that rely on the mass release of males to suppress mosquito populations will exert selective pressure on natural mating systems. Here, we investigate how mass releases might affect the mating behaviors of wild target populations. We highlight gaps in our understanding of both variation in these aspects of mosquito behavior and the evolutionary forces that maintain variation within and between populations. We provide a mathematical framework for integrating mosquito mating ecology into models of population suppression. Given that these strategies are being increasingly deployed, anticipating and managing evolutionary responses of target population behavior should be a priority for research.
Genetically modified mosquitoes released in the US: How they can prevent disease outbreaks
34732TOI Lifestyle Desk, Times of India, 2025-04-02 16:42:21.
The menace of mosquito-borne illnesses is growing in the US and the contributing factors range from climate change to their expanding habitats. The solution could lie in genetically modified mosquitoes that hold the capability to effectively control mosquito populations. Recently, genetically modified mosquitoes were released in Florida, US, following the successful trials in Brazil, the Cayman Islands, Panama, and Malaysia, where populations of aedes aegypti dropped by at least 90%. A significant step forward in preventing the deadly mosquito-borne illnesses, the bioengineered male aedes aegypti mosquitoes were introduced into the environment. While these deadly species make up for 4% of the total local mosquito population, they are enough to wreak havoc. It is to be noted that female aedes aegypti mosquitoes are the primary vectors that can transmit dengue, Zika, yellow fever, and chikungunya viruses to humans.
Exploring the ecology of malaria mosquitoes in São Tomé and Príncipe
34636Lisa Chamberland, Outreach Network for Gene Drive Research, 2025-03-21 14:28:58.
As part of our work to develop new genetic approaches for malaria control, the University of California Malaria Initiative (UCMI) is studying mosquito movement and breeding patterns in São Tomé and Príncipe. In a study published last year, we investigated the dispersal dynamics of Anopheles coluzzii – the only malaria vector on this island nation. Our recent study examines how environmental factors influence A. coluzzii breeding sites and shape mosquito dispersal across São Tomé and Príncipe. Understanding movement and interactions between mosquito populations is key to designing malaria control strategies. The data collected will also offer key insights that will guide the design of potential field evaluations of the technology we are working to develop. To determine the most suitable habitats for A. coluzzii, we used computer modeling to analyze environmental conditions such as temperature, elevation, and human population density. Our results show that the northeastern regions of both São Tomé and Príncipe islands provide the most suitable conditions for A. coluzzii larval development, with lower elevations and higher human population densities likely contributing to greater habitat availability. Interestingly, our climate modeling suggests that the mosquito’s geographic distribution on the islands will remain largely unchanged under current climate projections, even without additional interventions.
Making sex deadly for insects could control pests that carry disease and harm crops
34559Bill Sullivan, The Conversation, 2025-03-04 17:08:29.
Insects do a lot more harm than ruining picnics. Some insects spread devastating diseases, while others cause staggering economic losses in agriculture. To control some of these pests, scientists are developing males that make sex a deadly event. The stakes are high. Mosquitoes carry viruses such as dengue, West Nile and Zika, as well as parasites that cause malaria. Researchers estimate that mosquitoes have caused the deaths of 52 billion people overall – nearly half of all the humans that have ever lived. Other insects cause major crop damage, jeopardizing the food supply and driving up prices. According to the Food and Agriculture Organization of the United Nations, 20% to 40% of global crop production is lost to pests annually at a cost of US$70 billion. Pesticides have been the front-line defense against insects, but many bugs have evolved resistance to these chemicals. Some pesticides can indiscriminately kill beneficial insects, harm the environment and endanger human and animal health. Some researchers worry that certain pesticides can cause cancer or have damaging effects on human nervous and endocrine systems. I’m a microbiology researcher studying infectious disease. New solutions that do not harm humans and the environment to control disease-carrying insects and agricultural pests could lead to fewer people contracting dangerous diseases. In the past few years, a variety of genetic engineering approaches have emerged as promising tactics to combat problematic insects.
Assessment of drive efficiency and resistance allele formation of a homing gene drive in the mosquito Aedes aegypti
34261Yang, X., Xu, X., Chen, Y. et al., Journal of Pest Science, 2025-01-14 09:57:33.
Aedes aegypti, known for transmitting viruses such as dengue, Zika and yellow fever, poses a significant public health threat. Conventional insecticides give rise to a range of issues, including ecological contamination and insect resistance. Hence, there is a pressing demand for environmentally-friendly, safer and more efficacious strategies for mosquito control. With the rapid advancement of the CRISPR/Cas9 system in gene function exploration and pest population control, substantial progress has been achieved in utilizing CRISPR/Cas9-based gene drive systems across various mosquito species. Only a few studies on gene drive technology have been conducted in Ae. aegypti. In this study, we constructed two complete drives for Ae. aegypti with different Cas9 promoters, each targeting kmo. Our drive based on PubCas9 had limited activity, but one with ExuCas9 exhibited super-Mendelian inheritance rates of approximately 60%. We observed low but detectable somatic activity of the drive and no evidence of maternally deposited Cas9. Germline resistance allele formation rates were similar to drive conversion rates, but most wild-type alleles in the germline remained uncut. Injections into the ExuCas9 drive line had 100% knockout efficiency among surviving offspring at three separate target genes. These results support the development and application of novel genetic pest control technologies aimed at combating Ae. aegypti.
Genetically Engineered Male Insects Shorten Their Mates’ Lifespans
34253Sneha Khedkar, The Scientist, 2025-01-13 15:13:56.
On a still night, as the air is thick with silence, the sharp, whining buzz of a mosquito shatters the calm. These blood-sucking insects that disturb people’s deep slumber are also responsible for spreading diseases such as dengue, chikungunya, malaria and Zika fever, which affect millions of people each year worldwide. Given the harmful effects of pesticides on the environment, combined with the emergence of mosquitoes resistant to pesticides, scientists are looking for alternative environment-friendly approaches for pest management. Now, researchers have developed a new population control method where male insects carrying toxic proteins can poison disease-spreading females during mating. The results, published in Nature Communications, describe a genetic biocontrol method that offers a fast and effective solution to managing pests. Such approaches are not entirely new. In the 1950s, when researchers mated female insects with radiologically sterilized males, they did not produce offsprings, reducing the next generation’s population. More recently, scientists propagated transgenes in insects that lower the fitness of future generations, resulting in decreased insect population. Although such methods are promising, they require at least one generation to take effect: Female insects may not produce offsprings, but they can continue transmitting infections. “As we’ve learned from COVID-19, reducing the spread of these diseases as quickly as possible is important to prevent epidemics,” said study author Samuel Beach, a graduate student in biologist Maciej Maselko’s lab at Macquarie University, in a press release.
‘Toxic Male Technique’ promises faster biocontrol of mosquito populations
34223Macquarie University, Phys.org, 2025-01-07 20:57:52.
A new biological pest control method that targets the lifespan of female insects could significantly reduce the threat of insect pests such as disease-carrying mosquitoes by offering faster and more effective results than current methods. Described in Nature Communications, the technique developed by researchers in Applied BioSciences and the ARC Center of Excellence in Synthetic Biology at Macquarie University is a new approach called the Toxic Male Technique (TMT). It works by genetically engineering male insects to produce insect-specific venom proteins in their semen. When these males mate with females, the proteins are transferred, significantly reducing female lifespan and their ability to spread disease. Insect pests pose a growing threat to global health and agriculture, causing hundreds of thousands of deaths, millions of infections, and costing billions in health care and crop damage annually. In mosquitoes like Aedes aegypti and Anopheles gambiae, only the females bite and transmit diseases such as malaria, dengue, Zika, chikungunya disease and yellow fever. Pesticides face declining effectiveness due to resistance and have caused harm to non-target species and ecosystems. Genetic biocontrol has emerged as a promising alternative. Current techniques like the Sterile Insect Technique (SIT) or insects carrying lethal genes (RIDL) work by releasing massive numbers of sterilized or genetically modified males to mate with the wild females. While these mated females produce no offspring or only male offspring, they continue to blood-feed and spread disease until they die naturally—meaning populations of biting females only decrease when the next generation emerges. By immediately reducing the biting female population, TMT offers significant advantages over competing genetic biocontrol methods. "As we've learned from COVID-19, reducing the spread of these diseases as quickly as possible is important to prevent epidemics," says lead author Sam Beach.
Should We Unleash GMO Mosquitoes?
34051Brooke Borel and Anna Rothschild, Entanglements, 2024-12-16 14:26:29.
In this episode of Entanglements, hosts Brooke Borel and Anna Rothschild discuss the ethics and risks of genetically modified (GMO) mosquitoes. They explore differing expert opinions, focusing on technologies like gene drives and sterile males, examining ecological and safety concerns while debating whether releasing GMO insects is ultimately beneficial.
Variable effects of transient Wolbachia infections on alphaviruses in Aedes aegypti
33429Brittany L. Dodson, Sujit Pujhari, et al., PLoS Neglected Tropical Diseases, 2024-11-05 11:32:58.
Wolbachia pipientis (= Wolbachia) has promise as a tool to suppress virus transmission by Aedes aegypti mosquitoes. However, Wolbachia can have variable effects on mosquito-borne viruses. This variation remains poorly characterized, yet the multimodal effects of Wolbachia on diverse pathogens could have important implications for public health. Here, we examine the effects of transient somatic infection with two strains of Wolbachia (wAlbB and wMel) on the alphaviruses Sindbis virus (SINV), O’nyong-nyong virus (ONNV), and Mayaro virus (MAYV) in Ae. aegypti. We found variable effects of Wolbachia including enhancement and suppression of viral infections, with some effects depending on Wolbachia strain. Both wAlbB- and wMel-infected mosquitoes showed enhancement of SINV infection rates one week post-infection, with wAlbB-infected mosquitoes also having higher viral titers than controls. Infection rates with ONNV were low across all treatments and no significant effects of Wolbachia were observed. The effects of Wolbachia on MAYV infections were strikingly strain-specific; wMel strongly blocked MAYV infections and suppressed viral titers, while wAlbB had more modest effects. The variable effects of Wolbachia on vector competence underscore the importance of further research into how this bacterium impacts the virome of wild mosquitoes including the emergent human pathogens they transmit.
Engineering Resilient Gene Drives Towards Sustainable Malaria Control: Predicting, Testing and Overcoming Target Site Resistance
33379Ioanna Morianou, Lee Phillimore, Bhavin S. Khatri,, bioRxiv, 2024-11-04 13:56:24.
CRISPR-based gene drives are selfish genetic elements with the potential to spread through entire insect populations for sustainable vector control. Gene drives designed to disrupt the reproductive capacity of females can suppress laboratory populations of the malaria mosquito. However, any suppressive intervention will inevitably exert an evolutionary pressure for resistance. Here, we present a pipeline for the accelerated discovery, engineering, and testing of both natural and drive-induced variants that could reverse gene drive spread. We applied our method to stress-test a highly effective gene drive that has evaded resistance in all laboratory-contained releases to date, known as Ag(QFS)1. We showed that previously undetected resistant alleles can arise at low frequency, and discovered novel, partially resistant alleles that can perturb drive-invasion dynamics. We then engineered next-generation gene drives that can actively remove resistant alleles by targeting several highly conserved and non-overlapping sites in the female-specific exon of the doublesex gene. Our models predict that such gene drive designs could suppress large, natural populations of the malaria mosquito in the field.
Man Vs. Mosquito
33147Aman Vora, Brown Political Review, 2024-10-31 08:49:52.
It is a middle school math teacher’s favorite trivia question: What is the world’s deadliest animal? After images of a hunting tiger or towering gorilla flash through our imagination, we remember that it is the humble mosquito, whose terrible impact on human lives and healthcare systems is only projected to grow. As carbon emissions continue to rise with no plateau in sight, one oft-forgotten implication of increasing global temperatures is the devastating impact they will wreak on public health, with historically ignored diseases now able to thrive in a new, warmer climate. As global temperatures barrel toward the preferred range for mosquitoes, the number of individuals at risk for contracting malaria and dengue fever may increase by four to seven billion by 2070 relative to 1999. This threat is already a reality. Take dengue, for example: From 1980 to 1989, there were 1.5 million reported cases globally. Compare that to 2019 alone, when 5.2 million cases were reported. World Health Organization (WHO) officials described this astronomical rise in dengue as a “canary in the coalmine of the climate crisis.” No longer will mosquito-borne diseases primarily threaten equatorial regions—northern cities globally are all at risk due to the rise of Aegypti and Anopheles mosquitoes. Science: 0. Mosquitoes: 1. From bed nets to insecticides, progress is being made to combat this terrifying rise. But the current generation of anti-mosquito tools is not aggressive enough to mitigate this deadly problem: Bed nets do little to stop Aegypti, which primarily feed on blood during the day, and toxic insecticides have done little but harm the environment and drive mosquito resistance. In order to save lives from this man-made and mosquito-driven catastrophe, humanity must embrace its most promising scientific technologies: genetic engineering and Wolbachia bacteria, conscious that we are fighting against both Mother Nature and human nature itself.
Scientists explore new solutions to fight insecticide resistance, emerging mosquito species
31587Milliam Murigi, People Daily, 2024-09-17 12:05:17.
Africa has long been the epicenter of malaria, battling the deadly disease with a combination of strategies, including insecticide-treated bed nets and indoor spraying. However, the landscape of this fight is rapidly changing. Mosquitoes are increasingly developing resistance to insecticides, undermining these critical interventions. Additionally, new mosquito species, previously not found in certain regions, are now making their presence felt, posing new threats and challenges. But what does the emergence of this double tragedy mean to the continent and what actions are being taken? Dr Willy Kiprotich Tonui, EBS, the Chairman and Executive Director at Environmental Health Safety who also doubles up as the Founder and Head of the Secretariat at the African Genetic Biocontrol Consortium says that the emergence of these challenges means that new solutions must be developed and that is why scientists have been working day and night to come up with new solutions. So far new compounds, DIF-1(+3), which has demonstrated significantly stronger growth inhibitory effects against Plasmodium falciparum have been synthesized, including strains resistant to chloroquine and artemisinin. This compound showed near-complete suppression of parasite growth in vivo tests, indicating its potential as a new treatment option in areas with high levels of drug resistance. “New insights into how malaria parasites invade host cells have also been revealed. This is useful in understanding mechanisms that can aid in developing targeted treatments and vaccines to prevent the parasite from establishing infection in the first place,” says Dr Tonui.
Scientists want to use mosquito stomach bacteria to end malaria
31201Chia-Yu Chen & Shüné Oliver, Alliance for Science, 2024-08-27 14:05:18.
The months of September to May are an unfortunate season in South Africa: malaria season. The mosquito-borne disease is found in the north-eastern districts of KwaZulu-Natal, Mpumalanga and Limpopo provinces. There are fewer malaria cases in South Africa compared to other African countries. The World Health Organization estimated there were over 10 million cases of malaria in Mozambique in 2022. South Africa, that country’s neighbor, recorded 5,183 malaria cases between September 2022 and August 2023. Its relatively low case numbers may be a result of South African health authorities’ excellent work in controlling the disease (control efforts began more than 120 years ago). The last major malaria outbreak in South Africa was in 2000, when more than 60,000 cases were recorded. Also notable was the 2017 outbreak, with 28,264 cases. This combination of control efforts and low numbers may mean that South Africans think malaria is not something they need to worry about unless they travel to provincial hotspots in the months of September to May. But it remains a disease of concern – not just within the country’s borders, but in the broader southern African region. Many researchers like ourselves are working towards eliminating or even, one day, totally eradicating the disease. “Elimination” doesn’t mean there will be no malaria in the region at all. Instead, it would mean that local mosquitoes no longer spread the disease in South Africa. The reason that South Africa has not fully eliminated malaria is precisely because its local mosquito populations are still transmitting the disease. In fact, in 2023, about 17 percent of people who got sick from malaria had caught it in South Africa and not from travelling to neighboring African countries. Scientists are using and developing many different “weapons” in the fight against malaria. Our approach involves using mosquitoes’ own gut bacteria to prevent them from spreading malaria. This is a form of biocontrol, which involves the use of living organisms or natural substances to control harmful pests. The groundwork we’re laying with this ongoing research will, we believe, allow us and other scientists to create a powerful malaria-beating tool.
Malaria & Dengue; distinguishing mosquito-borne diseases
31178Grace Matheka, HapaKenya, 2024-08-25 20:26:45.
World Mosquito Day is commemorated every year on the 20th of August. The day brings an opportunity to raise awareness on the dangers posed by mosquito-borne diseases like malaria and dengue, and the ongoing efforts to combat them. Both malaria and dengue are transmitted by female mosquitoes and cause severe illness in humans. The two diseases have some similarities, and mosquito species are often confused by patients and medical personnel. Malaria is a leading cause of death in the world, with 200 million cases reported every year worldwide, leading to 600,000 deaths. Most of these deaths happen in Africa, affecting children and pregnant women most. In 2022, WHO reported that Africa was home to 94% of malaria cases at 233 million and 95% at 580 000 of malaria deaths. Children under five accounted for about 78% of all malaria deaths.
Genetically Modified Wolbachia mosquitoes help reduce virus transmission
31461Precision Vaccinations, 2024-08-20 10:33:21.
Every year on World Mosquito Day, diseases spread by mosquitoes, which account for over 17% of all infectious diseases and lead to more than 700,000 deaths annually, are highlighted. Parasites, bacteria, or viruses can cause these diseases, including chikungunya, malaria, dengue, Zika, and yellow fever. While some diseases can be prevented with innovative travel vaccines, some can not. This is why the World Mosquito Program exists today. According to the World Mosquito Program, the Wolbachia method is vital in fighting mosquito-borne diseases and protecting communities worldwide. This program can reduce the number of Aedes aegypti mosquitoes. When male Ae. aegypti mosquitoes with Wolbachia mate with wild female mosquitoes that do not have Wolbachia. The eggs will not hatch. Because the eggs don't hatch, the number of Ae. aegypti mosquitoes decreases. They do this by breeding with wild mosquitoes until, over several generations, they replace the local mosquito population. This means Wolbachia mosquitoes help decrease the risk of dengue, Zika, chikungunya, and yellow fever outbreaks. The World Mosquito Program is currently operating in 13 countries—Australia, Brazil, Colombia, Indonesia, Sri Lanka, Honduras, Laos, Vietnam, Kiribati, Fiji, Vanuatu, New Caledonia, and Mexico—and protects more than 11.4 million people. In the United States, communities in Texas, Florida, and California have released mosquitoes with Wolbachia over the past seven years and a significant decrease in Ae. aegypti mosquitoes have been reported. In 2023, the state of Hawaiʻi also launched a Wolbachia program. Most importantly, the U.S. CDC says no data suggests that Wolbachia bacteria harm people, animals, or the environment. Let's hope locally-acquired chikungunya, dengue, and malaria cases soon become distant memories as disease-carrying mosquitos disappear.
Scientists’ novel technology to conserve mosquitoes
31459Milliam Murigi, People Daily, 2024-08-20 09:24:48.
As the world celebrates World Mosquito Day today, scientists have introduced a revolutionary technology that could conserve mosquitoes instead of killing them while eliminating some of the diseases transmitted by mosquitos. Known as gene drive technology, this innovative approach promises to eliminate malaria one of the diseases that is transmitted by mosquitos without harming the mosquito population a crucial aspect that could make this solution both effective and environmentally sustainable. “Gene drives have been successfully tested in laboratory settings to reduce mosquito fertility and spread resistance genes against the malaria parasite. There are field trials and pilot studies underway to test the effectiveness and safety of gene drives in real-world environments,” says Dr Willy Tonui. Tonui, the Chairman and Executive Director at Environmental Health Safety (EHS Consultancy Ltd) also doubles up as the Founder and Head of the Secretariat at the African Genetic Biocontrol Consortium.
Mosquitoes On The Run Due To Wolbachia Programmes.
30949Anonymous, St Kitts and Nevis Observer, 2024-07-25 18:53:51.
Dengue is becoming an increasingly common disease in Central America and the Caribbean, according to PAHO, even as deaths from the mosquito-born condition have fallen in recent years due to improved identification of the condition and medical care. However the World Mosquito Progam is reporting considerable success in reducing mosquito born diseases like Dengue and reporting remarkable results from countries such as Colombia and El Salvador by using something called the Wolbachia method. What is this? Wolbachia are safe, naturally occurring bacteria present in up to 50% of species, including some mosquitoes. Wolbachia has evolved to live inside the cells of many insect species. It has maintained this lifestyle for tens of thousands of years. Wolbachia cannot survive outside of insect cells because it does not have the necessary machinery to replicate itself without help from the insect host. This means Wolbachia cannot survive in the environment (e.g. the air or soil). Wolbachia is not a virus or a parasite. It is not a “gene drive”. Wolbachia has never been genetically modified by scientists. However, Wolbachia is not usually found in the Aedes aegypti mosquito, the primary species responsible for transmitting viruses such as dengue, Zika, chikungunya and epidemic yellow fever.
Former minister wants modified mosquitoes to fight dengue spread
30933Otto Carrington, Trinidad and Tobago Guardian, 2024-07-24 15:53:02.
With this country reporting more dengue cases this year than last year and two dengue deaths reported so far, former health minister Dr Fuad Khan is urging the Government to consider genetically modified mosquitoes to help fight the spread of the disease. Khan, who served as Health Minister for one term, proposed in 2011 that genetically modified (GM) male mosquitoes, which have been successfully used in other countries to combat the Aedes aegypti mosquitoes (which cause dengue fever), could be a solution. However, this project never materialised. Speaking on CNC3’s The Morning Brew, Khan again suggested that genetically modified male mosquitoes could be effectively used. “I think that should be looked at again because it has been used successfully in Brazil and Florida.Genetically modified male mosquitoes breeding with female Aedes aegypti is an approach we need to consider. It’s important to find a scientific method to deal with these mosquitoes,” Khan said. He also called for updated legislation to ensure that people are mandated to keep their surroundings clean. He said if they fail to do so, they should be penalised. “It’s crucial to find a scientific way to manage Aedes aegypti mosquitoes. Breeding grounds are straightforward. Everyone should maintain their surroundings, and there should be legislation enforcing this. If the insect vector control team finds that you’re not complying with warnings to clean your yard, you’re endangering public safety,” he stated. Khan added, “Spraying doesn’t work effectively because the breeding ground for mosquitoes is in stagnant water and drains. When you spray, you might kill the mosquitoes flying around temporarily, but you don’t address the larvae in the water. Spraying only kills what’s on the surface.”
Effects of a blood-free mosquito diet on fitness and gonotrophic cycle parameters of laboratory reared Anopheles gambiae sensu stricto
30929Mosi, F.A., Rutha, I., Velez, R. et al., Parasites and Vectors, 17. 2024-07-24 15:43:32.
The current rise of new innovative tools for mosquito control, such as the release of transgenic mosquitoes carrying a dominant lethal gene and Wolbachia-based strategies, necessitates a massive production of mosquitoes in the insectary. However, currently laboratory rearing depends on vertebrate blood for egg production and maintenance. This practice raises ethical concerns, incurs logistical and cost limitations, and entails potential risk associated with pathogen transmission and blood storage. Consequently, an artificial blood-free diet emerges as a desirable alternative to address these challenges. This study aims to evaluate the effects of a previously formulated artificial blood-free diet (herein referred to as BLOODless) on Anopheles gambiae (An. gambiae s.s.; IFAKARA) gonotrophic parameters and fitness compared with bovine blood. The study was a laboratory-based comparative evaluation of the fitness, fecundity and fertility of An. gambiae s.s. (IFAKARA) reared on BLOODless versus vertebrate blood from founder generation (F0) to eighth generation (F8). A total of 1000 female mosquitoes were randomly selected from F0, of which 500 mosquitoes were fed with bovine blood (control group) and the other 500 mosquitoes were fed with BLOODless diet (experimental group). The feeding success, number of eggs per female, hatching rate and pupation rate were examined post-feeding. Longevity and wing length were determined as fitness parameters for adult male and female mosquitoes for both populations. While blood-fed and BLOODless-fed mosquitoes showed similar feeding success, 92.3% [95% confidence interval (CI) 89.7–94.9] versus 93.6% (95% CI 90.6–96.6), respectively, significant differences emerged in their reproductive parameters. The mean number of eggs laid per female was significantly higher for blood-fed mosquitoes (P < 0.001) whereas BLOODless-fed mosquitoes had significantly lower hatching rates [odds ratio (OR) 0.17, 95% CI 0.14–0.22, P < 0.001]. Wing length and longevity were similar between both groups. This study demonstrates the potential of the BLOODless diet as a viable and ethical alternative to vertebrate blood feeding for rearing An. gambiae s.s. This breakthrough paves the way for more efficient and ethical studies aimed at combating malaria and other mosquito-borne diseases.
Culex-Transmitted Diseases: Mechanisms, Impact, and Future Control Strategies using Wolbachia
31030Madhav, M.; Blasdell, K.R.; Trewin, B.; Paradkar, P.N.; López-Denman, A.J., Viruses, 16:1134. 2024-07-15 11:40:32.
Mosquitoes of the Culex genus are responsible for a large burden of zoonotic virus transmission globally. Collectively, they play a significant role in the transmission of medically significant diseases such as Japanese encephalitis virus and West Nile virus. Climate change, global trade, habitat transformation and increased urbanisation are leading to the establishment of Culex mosquitoes in new geographical regions. These novel mosquito incursions are intensifying concerns about the emergence of Culex-transmitted diseases and outbreaks in previously unaffected areas. New mosquito control methods are currently being developed and deployed globally. Understanding the complex interaction between pathogens and mosquitoes is essential for developing new control strategies for Culex species mosquitoes. This article reviews the role of Culex mosquitos as vectors of zoonotic disease, discussing the transmission of viruses across different species, and the potential use of Wolbachia technologies to control disease spread. By leveraging the insights gained from recent successful field trials of Wolbachia against Aedes-borne diseases, we comprehensively discuss the feasibility of using this technique to control Culex mosquitoes and the potential for the development of next generational Wolbachia-based control methods.
FILMS: Gene drive mosquitoes for malaria control
30894Sarah Hartley and Tom Law, Gene Drive Governance, 2024-07-09 08:50:21.
Gene drive mosquitoes for malaria control is a short documentary film that is beautifully shot in Uganda and explores Ugandan stakeholders’ hopes for gene drive mosquitoes – a radical new tool that offers a way to eliminate or change the mosquitoes that cause malaria. Uganda is one of the first countries in the world preparing for field trials for gene drive mosquitoes and malaria is the main cause of death in Uganda, so the stakes are high. The film builds on social science research at the University of Exeter in the UK and Makerere University in Uganda and shows how complex it is to govern gene drive.
Mosquito population structure and gene-drive
30499Heredity Podcast, 2024-06-04 20:59:37.
Gene-drives hold great potential for the control of biological pests, but first they need to be thoroughly tested under appropriate conditions. In this episode we discuss some new work assessing whether mosquito populations in Northern Australia could be used to test a gene-drive targeting malaria mosquitoes.
Djibouti Unleashes Controversial Genetically Modified Mosquitoes
30497Palki Sharma, Firstpost, 2024-06-04 20:55:28.
Djibouti is combatting malaria by employing a unique tactic: utilising mosquitoes to battle mosquitoes. The East African nation has released tens of thousands of genetically engineered mosquitoes armed with a "self-limiting" gene. This bioengineered gene aims to curb mosquito populations by terminating their offspring. However, concerns have been voiced about the experimental nature of this genetic modification technique and the absence of adequate regulation. While Burkina Faso, Brazil, Panama, and India have ventured into similar endeavors, the efficacy and long-term implications of such interventions remain uncertain. The debate persists: are genetically modified mosquitoes a daring gamble or a promising solution to eradicate deadly diseases like malaria?
Genetically modified mosquitoes to fight malaria
30493The Naked Scientists, 2024-06-04 17:15:48.
Genetically engineered mosquitoes are taking to the air in an experiment to attempt to curtail malaria in Djibouti. The tiny African nation all but eliminated malaria just over a decade ago. But rising population and urbanisation has seen disease cases skyrocketing again, making it an ideal venue to test the technology, which uses a genetic trick to kill off selectively female mosquitoes; this leaves the males - which don’t bite humans - unharmed to breed and pass on the trait to other members of the species.
Investigating the ecological role of malaria mosquitoes
30358Talya D. Hackett, Outreach Network for Gene Drive Research, 2024-05-21 20:22:50.
A team of entomologists and ecologists at the University of Ghana have been working with colleagues from the University of Oxford and the Centre for Biodiversity Genomics at the University of Guelph on a groundbreaking project to investigate the potential ecological consequences of reducing the population of the malaria mosquito Anopheles gambiae. This research is a key part of our work at Target Malaria, a not-for-profit research consortium whose aim is to develop new tools to reduce malaria transmission. The “ecological observatory project” studies the ecological interactions between An.gambiae and other species in the local ecosystem, including its larval competitors and predators, adult predators, and plant species that it might visit for sugar meals. By collecting data on the community ecology surrounding these mosquitoes, we can predict the effect, if any, that reducing their numbers could have on the ecosystem.
Gene drive mosquitoes designed to eliminate malaria – but governance is complex, new film shows
29897Russell Parton, University of Exeter, 2024-05-07 16:59:05.
A radical new biotechnology could eliminate the mosquitoes that cause malaria, but in Uganda – where malaria is the leading cause of death – a lack of information and debate is undermining public debate on the issue. Professor Sarah Hartley’s new research documentary Gene Drive Mosquitoes for Malaria Control, which will be screened at Exeter Phoenix on 29 April, looks at this potentially game-changing technology through conversations with Ugandan stakeholders and explores the complexities of governance. Gene drive mosquitoes are being researched in Uganda by scientists at the Ugandan Virus Research Institute, and could soon be trialled in the wild – making Uganda one of the first countries to do so. Gene drive targets the particular genes in the malaria-transmitting female mosquito, making it unable to reproduce or transmit malaria. But unlike in other forms of genetic modification, the altered gene is inherited by more than 95% of offspring, which means the trait increases over time – allowing it to spread through a whole population. This means we could change the mosquito at a scale never seen before. Gene drive offers the possibility of controlling malaria, but the decision to release gene drive mosquitoes into the wild hinges not only on the science but on social, political and environmental issues and the support of the public.
How to Use Genetic Biocontrol to Manage Insect Pests
29891Scientific Animations Without Borders, YouTube, 2024-05-07 16:41:35.
Pest insects often transmit disease to humans and animals and destroy crops. Controlling these pests can improve human health and increase agricultural production. Pest insects are often controlled by releasing other insects into the environment that will specifically kill the pests. This method of pest control is called biological control and is environmentally friendly because it reduces reliance on chemical insecticides and targets only the pest insects. Genetic biocontrol is a type of biological control where the released insects are the same species as the pest but with critical genetic differences and traits that affect their reproduction or lifespan.
How could genetic approaches be integrated in the malaria toolkit?
29889Damaris Matoke-Muhia, Outreach Network for Gene Drive Research, 2024-05-07 16:29:20.
The Outreach Network for Gene Drive Research organized a symposium on the margins of the Multilateral Initiative on Malaria (MIM Society)’s 8th Pan-African Malaria Conference held last week in Kigali, Rwanda. The event explored how novel genetic approaches could be integrated into the malaria toolkit and contribute to end malaria. I had the pleasure of participating in the Network’s symposium “Integrating genetic approaches in the malaria toolkit” as a panellist alongside Lucy Okell, Imperial College London and Isabelle Coche, Secretariat of the Outreach Network for Gene Drive Research. The session was chaired by El Hadji Amadou Niang, Pan-African Mosquito Control Association (PAMCA). Speakers discussed the potential of genetic approaches such as gene drive technologies to offer a sustainable, long term and cost-effective solution that could, in the context of integrated approaches to malaria control, contribute to the elimination of the disease. Presentations emphasized the need for collaboration, effective governance, multi-stakeholder engagement and strategic planning to support the effective integration of gene drive technologies into malaria control strategies.
To fend off aggressive female mosquitoes, L.A. is releasing thousands of sterile males
29882Evan Bush, NBC News, 2024-05-07 15:46:02.
In Los Angeles, those who wage war on mosquitoes are adding a weapon to their arsenal: more mosquitoes. The Greater Los Angeles County Vector Control District on Thursday launched a pilot program to release tens of thousands of irradiated, lab-raised mosquitoes into the local environment. These mosquitoes are all male and have been sterilized by the radiation, so the hope is that they will find wild female mates and impregnate them with dead-end sperm, rendering the resulting eggs worthless. The target is a particular species, Aedes aegypti. The insects, which began to populate Los Angeles County in 2014, have evolved to hone in on one thing — you. “Thousands of years ago, a strain of Aedes aegypti moved in close to people and started to specialize to live near houses and bite people,” said Daniel Hahn, a professor in the University of Florida’s Department of Entomology and Nematology. “They’re characterized as aggressive nuisance biters because they’ll bite you all day long.” Aedes Aegypti thrive in backyards and make their homes in small containers like bottle caps and dog bowls. They can carry worrisome diseases like yellow fever, Chikungunya, Zika and dengue. “We know our residents are suffering,” said Susanne Kluh, the general manager of the Greater Los Angeles County Vector Control District, which serves 6 million people and has more than 90 full-time staffers. The district on Thursday released about 20,000 sterile male mosquitoes, dyed to appear fluorescent under a black light, as part of its final pilot program test. Male Aedes Aegypti mosquitoes don’t bite, so experts say the program poses near-zero risk to humans.
Wolbachia infection-responsive immune genes suppress Plasmodium falciparum infection in Anopheles stephensi
29565Vandana V, Dong S, Sheth T, Sun Q, Wen H, Maldonado A, et al., PLoS Pathogens, 20. 2024-04-25 18:04:55.
Wolbachia, a maternally transmitted symbiotic bacterium of insects, can suppress a variety of human pathogens in mosquitoes, including malaria-causing Plasmodium in the Anopheles vector. However, the mechanistic basis of Wolbachia-mediated Plasmodium suppression in mosquitoes is not well understood. In this study, we compared the midgut and carcass transcriptomes of stably infected Anopheles stephensi with Wolbachia wAlbB to uninfected mosquitoes in order to discover Wolbachia infection-responsive immune genes that may play a role in Wolbachia-mediated anti-Plasmodium activity. We show that wAlbB infection upregulates 10 putative immune genes and downregulates 14 in midguts, while it upregulates 31 putative immune genes and downregulates 15 in carcasses at 24 h after blood-fed feeding, the time at which the Plasmodium ookinetes are traversing the midgut tissue. Only a few of these regulated immune genes were also significantly differentially expressed between Wolbachia-infected and non-infected midguts and carcasses of sugar-fed mosquitoes. Silencing of the Wolbachia infection-responsive immune genes TEP 4, TEP 15, lysozyme C2, CLIPB2, CLIPB4, PGRP-LD and two novel genes (a peritrophin-44-like gene and a macro domain-encoding gene) resulted in a significantly greater permissiveness to P. falciparum infection. These results indicate that Wolbachia infection modulates mosquito immunity and other processes that are likely to decrease Anopheles permissiveness to Plasmodium infection.
A naturally isolated symbiotic bacterium suppresses flavivirus transmission by Aedes mosquitoes
29561Liming Zhang et al., Science, 384. 2024-04-25 17:51:54.
Flavivirus diseases are increasing in incidence and prevalence owing to the urban proclivities of its Aedes mosquito vector species. Extirpation of mosquitoes is considered key for the control of several human diseases but often involves toxic chemicals that prompt mosquito resistance. As some biocontrol alternatives look promising in malaria campaigns, Zhang et al. examined the microbiota of Aedes mosquitoes for potential agents to control dengue and Zika virus transmission. The authors isolated a bacterium called Rosenbergiella_YN46 in Aedes albopictus mosquitos. The bacterium was fed to caged mosquitoes to establish stable gut infections, and it was found to prevent the insects from being infected by viruses and blocked viral transmission to mice.
African health ministers commit to concerted action to end malaria deaths
29556Felista Tarimo, Outreach Network for Gene Drive Research, 2024-04-25 17:39:16.
On March 6, health ministers from African countries with the highest burden of malaria met in Yaoundé, Cameroon, and signed a declaration committing to the fundamental principle “that no one should die from malaria.” The Declaration for Accelerated Malaria Mortality Reduction in Africa signals a unified commitment to achieving a future free from malaria deaths on the continent. Despite advances made in the fight against the disease over the last two decades, the World Health Organization (WHO) African Region still accounts for over 90% of malaria cases and deaths worldwide. The 11 signatory countries to the document, which are classified as High burden High Impact (HBHI) countries — and include the United Republic of Tanzania, where I live and work — account alone for 70% of the global malaria burden. The declaration underscores the urgency of addressing several emerging and persistent challenges hindering progress in the fight against malaria, such as inadequate funding, growing biological threats — including insecticide and drug resistance — as well as low access to and insufficient quality of health services. It outlines a comprehensive plan built on four pillars: stronger political will, data-driven strategies, best practices in action, and multisectoral collaboration. Central to the Yaoundé Declaration is Point 6, which emphasizes the pivotal role of research and innovation in the quest to end malaria deaths. The fight against malaria requires constant adaptation, and this declaration acknowledges the importance of developing new tools and technologies specifically tailored to the high-burden African context. The focus on research and innovation aligns perfectly with our work at Transmission Zero. Our international research programme — that brings together collaborators from several institutions in Tanzania, the United Kingdom and Switzerland — is working to develop new genetic technologies which could reduce malaria transmission by disrupting mosquitoes’ ability to transmit the malaria parasite to humans. If proven safe and effective, this approach could complement existing tools to achieve the vision of a world free from malaria.
Genetically modified mosquitoes could one day end malaria
29553Alexis Akwagyiram, Semafor, 2024-04-25 17:31:43.
Abdoulaye Diabaté, a scientist from Burkina Faso, is at the vanguard of efforts to eliminate malaria by editing the genetic makeup of male mosquitoes and releasing them in the wild to prevent the reproduction of female mosquito species that transmit malaria. The technique is known as “gene drive” technology. Malaria kills more than 600,000 people every year, most of whom are children in Africa. Research by Diabaté, who heads medical entomology and parasitology at Burkina Faso’s Research Institute in Health Sciences, earned him the 2023 Falling Walls Prize for Science and Innovation Management. He spoke to Semafor Africa ahead of a Ted Talk on ending malaria. Gene drive offers great promises as a vector control tool. The fact that it is self-sustaining, meaning that a relatively small release of modified mosquitoes are able to spread within a population and induce suppression. It allows targeting a large area in a cost effective and self-sustaining manner, reaching areas that are difficult to control with conventional methods.
Bacteria found in mosquito guts could help scientists fight dengue, Zika
29548Catherine Offord, Science, 2024-04-25 17:12:41.
A team in China probing the guts of local mosquitoes has found a potential helper in the fight against two human diseases. Researchers identified a new bacterium that disables the viruses responsible for dengue and Zika before they can establish an infection in the insects. Although early stage, the work, reported this week in Science, paves the way for studying the bacterium’s effect on disease transmission in the real world. It wouldn’t be the first time a microbe is used to thwart mosquito-borne diseases. About 15 years ago, researchers discovered that a different bacterium, Wolbachia, reduces the insects’ ability to transmit dengue, among other viruses. Following successful field trials, Wolbachia is now used to help control dengue in more than a dozen countries. But an extra weapon to help control mosquito-borne diseases is welcome—especially as the insects become resistant to current insecticides. The new study is “promising,” says Nsa Dada, a vector biologist at Arizona State University who was not involved in the work. “It’s important that we explore … new tools that can complement existing control measures.” Lacking proven treatments or widely available vaccines, dengue is the most common mosquito-borne viral disease worldwide, infecting some 400 million people each year. Although most cases are mild or asymptomatic, about one in 20 people who get sick develop severe dengue, which can be fatal.
Genetic and geographic population structure in the malaria vector, Anopheles farauti, provides a candidate system for pioneering confinable gene-drive releases
29098Ambrose, L., Allen, S.L., Iro’ofa, C. et al., Heredity, 2024-04-16 09:13:44.
Indoor insecticide applications are the primary tool for reducing malaria transmission in the Solomon Archipelago, a region where Anopheles farauti is the only common malaria vector. Due to the evolution of behavioural resistance in some An. farauti populations, these applications have become less effective. New malaria control interventions are therefore needed in this region, and gene-drives provide a promising new technology. In considering developing a population-specific (local) gene-drive in An. farauti, we detail the species’ population genetic structure using microsatellites and whole mitogenomes, finding many spatially confined populations both within and between landmasses. This strong population structure suggests that An. farauti would be a useful system for developing a population-specific, confinable gene-drive for field release, where private alleles can be used as Cas9 targets. Previous work on Anopheles gambiae has used the Cardinal gene for the development of a global population replacement gene-drive. We therefore also analyse the Cardinal gene to assess whether it may be a suitable target to engineer a gene-drive for the modification of local An. farauti populations. Despite the extensive population structure observed in An. farauti for microsatellites, only one remote island population from Vanuatu contained fixed and private alleles at the Cardinal locus. Nonetheless, this study provides an initial framework for further population genomic investigations to discover high-frequency private allele targets in localized An. farauti populations. This would enable the development of gene-drive strains for modifying localised populations with minimal chance of escape and may provide a low-risk route to field trial evaluations.
Talking About Gene Drive in Uganda: The Need for Science Communication to Underpin Engagement
29082Hartley, S., Stelmach, A., Opesen, C., Openjuru, G. L., and Neema, S., Science Communication, 2024-04-04 09:15:22.
Uganda may host the world’s first field trials of gene drive mosquitoes for malaria control. Global North discourses pre-suppose African publics have access to information about gene drive and are ready to make decisions about its governance. We explore assumptions about the availability of this information in Uganda. We find a paucity of information available combined with a strong desire for information from lay publics. We discuss these findings in the context of Ugandan information infrastructures and political sensitivities to genetic technologies. If Ugandans are to decide about gene drive, they need independent information about the science to underpin engagement.
Biotech company implements controversial offspring-killing method to address dengue fever: ‘Will show a reduction of 20%’
29069Jeremiah Budin, The Cool Down, 2024-04-02 11:44:22.
"We can get out of this state of emergency."
Uganda and Djibouti seek Friendly mosquitoes to fight malaria
29066Richard Wetaya, Alliance for Science, 2024-04-02 11:40:33.
According to Oxitec CEO Grey Frandsen, the Friendly technology platform was ideally equipped to produce a safe, sustainable solution to manage the Anopheles stephensi mosquito vector based on years of experience creating and deploying other Oxitec solutions at scale.
Between the lab and the Wild: Establishing the Potential of Gene Drive Mosquitoes for Malaria Control
29055Mäkelin, M., Science as Culture, 2024-04-02 09:42:13.
Malaria control has been one of the defining goals in global health.
On EAC’s GMO disharmony and little-known GM mosquito research
29025Gitura Mwaura, The New Times, 2024-03-19 13:18:15.
A meeting in Dar es Salaam in November 2022 sought to chart the legal way forward for the Target Malaria and Transmission Zero Project, as the research initiative is called.
Efficacy of Wolbachia-based mosquito control: Predictions of a spatially discrete mathematical model
29008David Dye, John W. Cain, PLoS One, 19. 2024-03-11 12:43:55.
Wolbachia is an endosymbiont bacterium present in many insect species. When Wolbachia-carrying male Aedes aegypti mosquitoes mate with non-carrier females, their embryos are not viable due to cytoplasmic incompatibility. This phenomenon has been exploited successfully for the purpose of controlling mosquito populations and the spread of mosquito-borne illnesses: Wolbachia carriers are bred and released into the environment. Because Wolbachia is not harmful to humans, this method of mosquito control is regarded as a safer alternative to pesticide spraying. In this article, we introduce a mathematical framework for exploring (i) whether a one-time release of Wolbachia carriers can elicit a sustained presence of carriers near the release site, and (ii) the extent to which spatial propagation of carriers may allow them to establish fixation in other territories. While some prior studies have formulated mosquito dispersal models using advection-reaction-diffusion PDEs, the predictive power of such models requires careful ecological mapping: advection and diffusion coefficients exhibit significant spatial dependence due to heterogeneity of resources and topography. Here, we adopt a courser-grained view, regarding the environment as a network of discrete, diffusively-coupled “habitats”—distinct zones of high mosquito density such as stagnant ponds. We extend two previously published single-habitat mosquito models to multiple habitats, and calculate rates of migration between pairs of habitats using dispersal kernels. Our primary results are quantitative estimates regarding how the success of carrier fixation in one or more habitats is determined by: the number of carriers released, sizes of habitats, distances between habitats, and the rate of migration between habitats. Besides yielding sensible and potentially useful predictions regarding the success of Wolbachia-based control, our framework applies to other approaches (e.g., gene drives) and contexts beyond the realm of insect pest control.
Aedes aegypti Controls Ae. aegypti: SIT and IIT—An Overview
29003Robert L. Aldridge; Seth Gibson; Kenneth J. Linthicum, Journal of the American Mosquito Control Association, 20:32-49. 2024-03-11 12:34:19.
The sterile insect technique (SIT) and the incompatible insect technique (IIT) are emerging and potentially revolutionary tools for controlling Aedes aegypti (L.), a prominent worldwide mosquito vector threat to humans that is notoriously difficult to reduce or eliminate in intervention areas using traditional integrated vector management (IVM) approaches. Here we provide an overview of the discovery, development, and application of SIT and IIT to Ae. aegypti control, and innovations and advances in technology, including transgenics, that could elevate these techniques to a worldwide sustainable solution to Ae. aegypti when combined with other IVM practices.
Flight Against Infections: The Role of Genetically Engineered Mosquitoes, with Dr. Stephanie James
28997EeKs on Health, YouTube, 2024-03-11 10:40:20.
In this episode of Causes or Cures, Dr. Eeks chats with Dr. Stephanie James about the potential use of genetically modified mosquitoes (GMMs) to fight diseases that mosquitoes carry and spread, such as Malaria and Dengue Fever. In the podcast, Dr. James provides an overview on GMMs, as well as what something called Gene Drive Modified Mosquitoes (GDMMs) are. She talks about the current state of research, testing, and describes the GeneConvene Global Collaborative "GeneConvene", which was created to advance best practices and informed decision making for developing GMMs and GDMMs. She talks about the potential benefits versus the potential risks, how they are conducting risk assessments, how they plan to test GMMs, the ethical and safety concerns, and how local communities will be included in the decision-making process.
Effectiveness evaluation of mosquito suppression strategies on dengue transmission under changing temperature and precipitation
28984Kaihui Liu, Shuanghui Fang, Qiong Li, et al., Acta Tropica, 2024-03-05 20:16:41.
Mosquito Control releases over 100K sterile male mosquitos to combat Aedes aegypti population
28978NBC2 News, 2024-03-05 14:41:50.
Mosquito Control releases over 100K sterile male mosquitos to combat Aedes aegypti population
CRISPR-mediated germline mutagenesis for genetic sterilization of Anopheles gambiae males
28970Smidler, A.L., Marrogi, E., Kauffman, J. et al., Scientific Reports, 14. 2024-03-05 13:54:40.
Rapid spread of insecticide resistance among anopheline mosquitoes threatens malaria elimination efforts, necessitating development of alternative vector control technologies. Sterile insect technique (SIT) has been successfully implemented in multiple insect pests to suppress field populations by the release of large numbers of sterile males, yet it has proven difficult to adapt to Anopheles vectors. Here we outline adaptation of a CRISPR-based genetic sterilization system to selectively ablate male sperm cells in the malaria mosquito Anopheles gambiae. We achieve robust mosaic biallelic mutagenesis of zero population growth (zpg, a gene essential for differentiation of germ cells) in F1 individuals after intercrossing a germline-expressing Cas9 transgenic line to a line expressing zpg-targeting gRNAs. Approximately 95% of mutagenized males display complete genetic sterilization, and cause similarly high levels of infertility in their female mates. Using a fluorescence reporter that allows detection of the germline leads to a 100% accurate selection of spermless males, improving the system. These males cause a striking reduction in mosquito population size when released at field-like frequencies in competition cages against wild type males. These findings demonstrate that such a genetic system could be adopted for SIT against important malaria vectors.
Gene Drive Systems To Control Aedes Aegypti Mosquitoes Make Headway
28966Joshua Ang, Outreach Network for Gene Drive Research, 2024-03-05 13:15:42.
Aedes aegypti mosquitoes are known vectors of several diseases, including dengue, chikungunya, yellow fever, and Zika, which impact millions of people worldwide each year. The effectiveness of existing insecticide-based methods to control this mosquito is threatened by growing insecticide resistance, underscoring the need to develop new approaches. The advent of CRISPR/Cas9 genome editing has reshaped the research and development landscape of new potential vector control tools, leading researchers to explore novel approaches, such as gene drive technologies. In the past few years, gene drive technologies have gained remarkable traction, particularly for their success in controlling major malaria mosquito vectors in laboratory settings. A gene drive is able to bias its own inheritance, facilitating the spread of a specific trait through a target population. This super-Mendelian pattern of propagation makes gene drive technology an efficient and cost-effective potential new method to control mosquitoes that transmit disease.
Taking the fight against disease to mosquitoes
28948Gregory Devine, Setopati, 2024-02-27 18:33:30.
In the medium term it's likely that suppression strategies involving self-limiting genetic modifications, Wolbachia infection and irradiation will be extended to a small number of our most important mosquito vectors of disease.
South American cities release mosquitoes to stem disease
28913Roberto González, SciDev.Net, 2024-02-20 19:48:12.
When Waldeir Barbosa da Silva explained to his family that he was going to release hundreds of thousands of mosquitoes into the open, infected with a bacterium, they were surprised. In Niterói, southeast Brazil, where da Silva lives, diseases spread by mosquitoes, such as dengue, chikungunya, and Zika, pose a serious public health problem. However, when mosquitoes carry the bacteria Wolbachia, naturally present in many insects, their ability to transmit these viruses decreases.
Off the news: Gene-altered mosquitoes to the rescue
28902Star Advertiser, 2024-02-20 15:13:49.
A legal attempt to block deployment of genetically modified mosquitoes in a Maui forest was rejected in Circuit Court on Tuesday — cause for celebration among those hoping to save near-extinct species of Hawaiian honeycreepers. State and federal wildlife officials plan a staged release of sterile male (nonbiting) mosquitoes on the high slopes of Haleakala, crowding out breeding males to reduce the insect population. Fortunately, the challenge to the program failed: Only a very few Hawaiian honeycreepers remain, and warmer temperatures have allowed the deadly disease-carrying mosquitoes to infiltrate the birds’ only remaining island haven.
Opinion: A cautionary tale of experimenting with genetically modified mosquitoes in Uganda
28900Barbara Ntambirweki, The Independent, 2024-02-20 14:44:38.
The Uganda Virus Research Institute is pressing forward with gene drive technology which provides a way to rapidly, permanently, and genetically modify wild animals or plants. Gene drive organisms, are a genetically modified organism (GMO) designed to spread a genetic modification through entire populations of wild or farmed species, and are promoted as a ‘solution’ to pressing problems in the fields of public health, ecology and agriculture. The capacity of gene drives to spread and persist in the environment presents novel biosafety and socio-economic concerns for both people and biodiversity. Several research projects in Africa are advancing in their experiments to develop genetically modified ‘gene drive’ mosquitoes to release into the environment as a public health intervention to combat malaria and some are already releasing GMO mosquitoes similar to those touted by Oxitec. In Africa, Burkina Faso, Ghana, Tanzania and Uganda have allowed experimentation towards gene drive in their countries where some of these are under the auspices of Target Malaria – a consortium of research institutions led by laboratories based at Imperial College in the United Kingdom funded by Bill and Melinda Gates Foundation. In Uganda, Target Malaria has entered in partnership with the Uganda Virus Research Institute and has commenced entomological mosquito collections from field sites around Kalangala and Mukono Districts.
Gene driver flies and quantum finance: News from Imperial
28872Bryony Ravate, Hayley Dunning, Imperial College London, 2024-02-13 16:54:58.
Researchers have created the first gene drive for the Mediterranean fruit fly (medfly), a global agricultural pest affecting food production. The team was led by Dr Nikolai Windbichler and Dr Angela Meccariello at Imperial's Department of Life Sciences, and included researchers from the University of East Anglia and the Hebrew University of Jerusalem. Gene drives are genetic modifications that preferentially spread throughout a species, and which are designed to reduce the population. No gene drives have been released in the wild yet, but versions in malaria-carrying mosquitos have been shown to be highly effective in the lab. This success prompted the researchers to look at other pest species that could be susceptible to similar interventions. The team were able to target the process of sex determination in medflies, creating a gene drive that transforms genetic females into fertile but harmless XX males. The proof-of-concept demonstrates how gene drives can be applied to insect pests in the same group as medflies. Dr Meccariello said: “Our results demonstrate the untapped potential for gene drives to tackle agricultural pests in an environmentally friendly and economical way.”
New gene-editing tools may help wipe out mosquito-borne diseases
28859Greg Allen, NPR, 2024-01-30 17:05:14.
In the age-old war of human versus mosquitoes, the bugs have been winning. At least 700,000 people die every year from mosquito-borne diseases such as malaria, dengue, West Nile and yellow fever. Global trade and climate change have helped disease-carrying species become established in places like Florida, California, and Texas. In parts of the U.S., dengue is now a persistent problem. Last year, for the first time in decades, Florida and Texas reported locally-acquired malaria cases. Maryland also had a case. But by using bioengineering, scientists have developed tools they believe may help control and possibly eradicate mosquitoes that carry dengue, malaria and other diseases. Andrea Leal, the head of mosquito control in the Florida Keys says, "The good news is we've got these emerging technologies that show great promise in reducing Aedes aegypti mosquitoes."
Scientists create first transgenic mosquito strain in Africa
28847CGTN Africa, 2024-01-28 13:15:53.
Scientists in Tanzania have created the first transgenic mosquito strain in Africa. This genetically modified strain aims to prevent malaria transmission.
The epidemiology of imported and locally-acquired dengue in Australia, 2012–2022
28826Asma Sohail, Katherine L Anders, Sarah L McGuinness, Karin Leder, Journal of Travel Medicine, 2024-01-23 17:13:52.
Dengue is the most important arboviral disease globally, and poses ongoing challenges for control including in non-endemic countries with competent mosquito vectors at risk of local transmission through imported cases. We examined recent epidemiological trends in imported and locally-acquired dengue in Australia, where the Wolbachia mosquito population replacement method was implemented throughout dengue-prone areas of northern Queensland between 2011–2019. Dengue is the most important arboviral disease globally, and poses ongoing challenges for control including in non-endemic countries with competent mosquito vectors at risk of local transmission through imported cases. We examined recent epidemiological trends in imported and locally-acquired dengue in Australia, where the Wolbachia mosquito population replacement method was implemented throughout dengue-prone areas of northern Queensland between 2011–2019. Dengue is the most important arboviral disease globally, and poses ongoing challenges for control including in non-endemic countries with competent mosquito vectors at risk of local transmission through imported cases. We examined recent epidemiological trends in imported and locally-acquired dengue in Australia, where the Wolbachia mosquito population replacement method was implemented throughout dengue-prone areas of northern Queensland between 2011–2019.
Maxizyme-mediated suppression of chikungunya virus replication and transmission in transgenic Aedes aegypti mosquitoes
28819Mishra P, Balaraman V, Fraser Jr. M, Frontiers in Microbiology, 14. 2024-01-23 14:40:52.
Chikungunya virus (CHIKV) is an emerging mosquito-borne pathogen of significant public health importance. There are currently no prophylactic vaccines or therapeutics available to control CHIKV. One approach to arbovirus control that has been proposed is the replacement of transmission-competent mosquitoes with those that are refractory to virus infection. Several transgene effectors are being examined as potentially useful for this population replacement approach. We previously demonstrated the successful use of hammerhead ribozymes (hRzs) as an antiviral effector transgene to control CHIKV infection of, and transmission by, Aedes mosquitoes. In this report we examine a maxizyme approach to enhance the catalytic activity and prevent virus mutants from escaping these ribozymes. We designed a maxizyme containing minimized (monomer) versions of two hRzs we previously demonstrated to be the most effective in CHIKV suppression. Three versions of CHIKV maxizyme were designed: Active (Mz), inactive (ΔMz), and a connected CHIKV maxizyme (cMz). The maxizymes with their expression units (Ae-tRNA val promoter and its termination signal) were incorporated into lentivirus vectors with selection and visualization markers. Following transformation, selection, and single-cell sorting of Vero cells, clonal cell populations were infected with CHIKV at 0.05 and 0.5 MOI, and virus suppression was assessed using TCID50-IFA, RT-qPCR, and caspase-3 assays. Five transgenic mosquito lines expressing cMz were generated and transgene insertion sites were confirmed by splinkerette PCR. Our results demonstrate that Vero cell clones expressing Mz exhibited complete inhibition of CHIKV replication compared to their respective inactive control version or the two parent hRzs. Upon oral challenge of transgenic mosquitoes with CHIKV, three out of the five lines were completely refractory to CHIKV infection, and all five lines tested negative for salivary transmission. Altogether, this study demonstrates that maxizymes can provide a higher catalytic activity and viral suppression than hRzs.
Mosquito makeover: Tahiti’s groundbreaking solution to disease
28823Atutahi Potaka-Dewes, Pacific Media Network, 2024-01-19 14:49:43.
Mosquitoes are responsible for transmitting such diseases as dengue, malaria, zika, chikungunya, or filariosis, causing millions of deaths worldwide. French Polynesia is taking a groundbreaking initiative to address public health concerns and demonstrate a commitment to finding environmentally friendly solutions to curb disease spread. Building on a successful decade-long pilot project on the atoll Teti’aroa, the innovative method involves the strategic release of sterilised male Aedes Aegypti mosquitoes. The process sees the release of sterile males that will "contaminate" females, rendering them sterile and thereby naturally reducing the proliferation of the disease-bearing insect population. The Louis Malardé Institute's entomology laboratory says they have now developed an X-ray device that can mass-sterilise the males.
Sex or poison? Genetic pest management in the 21st century
28782Luke Alphey, BMC Biology, 21:289. 2024-01-11 13:14:20.
Pests do enormous damage to human and animal health, to agriculture and to biodiversity, with mosquitoes transmitting pathogens, insect larvae eating crops or invasive rodents threatening the last island refuges of endangered birds. This commentary focuses on insects, particularly mosquitoes. However, most considerations apply equally to other pest species. Genetic pest management (GPM) is the use of genetics to control pests through mating of modified pests with their wildtype counterparts. This allows heritable traits to be transferred (“introgressed”) into the wild pest population. In principle, any sexually reproducing pest species can be targeted. The aim is to reduce harm done by the pest population, with typical intended outcomes overwhelmingly falling into two types: population suppression and population modification. For population suppression, one would introgress fitness-reducing traits, such as lethality or sterility, leading to reduction in the numerical size of the pest populations if spread into the target population at sufficiently high frequency. Population modification aims to reduce the harm done by the pest without large changes in the numerical size of the pest population, for example by reducing the ability to transmit disease (“vector competence”) of modified mosquitoes. If such traits, or the DNA sequences encoding them, can be sustained at sufficiently high allele frequency in the target population then the desired harm-reduction outcome should be achieved, by reduction in the number of pests or by reduction in the per-pest harm.
The mosquito knows no borders: Regional challenges for global confrontation in the dengue battle
28789Barçante JMdP, Cherem J, PLoS Neglected Tropical Diseases, 18. 2024-01-04 14:05:29.
Dengue fever is a neglected disease with a global impact, and its incidence and geographical reach are rapidly expanding. Global warming marked by higher average temperatures, precipitation, and longer periods of drought could prompt a record number of dengue fever infections worldwide, due to the thermal biology of mosquitoes. Additionally, increased movement of people, urbanization, and pressure on water and sanitation have driven the spread of dengue fever. The absence of access to tap water leads to an increased reliance on water-storing containers, which can facilitate the breeding of mosquitoes. Similarly, the lack of sanitation can contribute to the formation of small pools of stagnant water, serving as ideal breeding grounds for Aedes. While more prevalent in the tropical and subtropical regions, this viral infection, transmitted by Aedes aegypti and Ae. albopictus mosquitoes, poses a serious public health problem, with outbreaks increasing in number and severity worldwide. In Europe, Aedes mosquito vector species are established in about 22 countries, and dengue fever has been reported for over a decade. In addition to the factors mentioned earlier, the increase in mosquito breeding sites has been identified as a determining factor for the rise in the number of cases.
Gene drives, mosquitoes, and ecosystems: An interdisciplinary approach to emerging ethical concerns
28778Ricardo D. Moreno, Luca Valera, Cristián Borgoño, Juan Carlos Castilla, José Luis Riveros, Frontiers in Environmental Science, 11. 2023-12-28 22:14:12.
Gene drives are genetic elements that in sexually reproducing organisms spread faster than those transmitted through a Mendelian fashion. Since gene drives can be engineered to modify different aspects of physiology and reproduction, they have been proposed as a new and revolutionary tool to control vector-borne diseases, particularly those transmitted by the genera Anopheles and Aedes (Culicidae), such as malaria, Dengue and Zika virus. This approach may impact on human health by lowering the transmission of such devastating diseases. However, the release of genetically modified mosquitos (or other species) into the environment raises a series of questions related to the still incipient technology and our present understanding of the complex structure and dynamics of terrestrial and aquatic ecosystems. Moreover, there are ethical concerns about human interventions in natural ecosystems that may eventually impact our way of living or the ecosystems themselves. This work is an interdisciplinary approach that analyzes from a biological, philosophical, and theological perspective the potential ecological impacts on natural environments of the release of genetically modified species, focusing on gene drive-modified mosquitos. It includes theological approach from a Catholic point of view (although it could be easily shared by other Christians) because we hold that world religions give valuable insights even though not everyone may share their groundings. We conclude that the focal problem is the relationship between humans and nature, and the release of genetically modified species may change this relationship unpredictably. However, given the complex interactions in ecosystems, new approaches such as Earth Stewardship principles could provide new and more widely accepted answers involving biological, philosophical, and theological concepts that will help engaging all relevant actors to make a better world.
Gene Drive Technology Unlocks Innovative Potential Solutions At The Intersection Of Climate Change And Public Health
28705Krystal Birungi, African Media Agency, 2023-12-12 17:23:52.
The inaugural ‘Day of Health’ at the UN Climate Conference (COP-28) highlighted the dramatic impact of climate change on health, diseases and in particular on malaria. Heads of State and climate experts converged in Dubai to emphasise the indisputable link between climate and health, echoing WHO Director-General Dr. Tedros Adhanom Ghebreyesus’s statement that climate change is a pressing public health issue. As we grapple with the harsh reality of half a million lives lost annually to malaria, including a child succumbing every minute in Africa, it is imperative to integrate innovative solutions that address both the disease and its broader public health implications exacerbated by climate change.
Large-scale releases and establishment of wMel Wolbachia in Aedes aegypti mosquitoes throughout the Cities of Bello, Medellín and Itagüí, Colombia
28645Velez ID, Uribe A, Barajas J, Uribe S, Ángel S, Suaza-Vasco JD, et al., PLoS Neglected Tropical Diseases, 2023-12-05 10:11:27.
The wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and has been shown to reduce the transmission of dengue and other Aedes-borne viruses. Here we report the entomological results from phased, large-scale releases of Wolbachia infected Ae. aegypti mosquitoes throughout three contiguous cities located in the Aburrá Valley, Colombia. These results, from the largest contiguous releases of wMel Wolbachia mosquitoes to date, highlight the operational feasibility of implementing the method in large urban settings. Based on results from previous studies, we expect that Wolbachia establishment will be sustained long term. Ongoing monitoring will confirm Wolbachia persistence in local mosquito populations and track its establishment in the remaining areas.
Different mechanisms of X-ray irradiation-induced male and female sterility in Aedes aegypti
28570Zhang, H., Trueman, E., Hou, X. et al., BMC Biology, 21. 2023-11-29 14:14:21.
Aedes aegypti (Ae. aegypti) is the major vector that transmits many diseases including dengue, Zika, and filariasis in tropical and subtropical regions. Due to the growing resistance to chemical-based insecticides, biological control methods have become an emerging direction to control mosquito populations. The sterile insect technique (SIT) deploys high doses of ionizing radiation to sterilize male mosquitoes before the release. The Wolbachia-based population suppression method of the incompatible insect technique (IIT) involves the release of Wolbachia-infected males to sterilize uninfected field females. Due to the lack of perfect sex separation tools, a low percentage of female contamination is detected in the male population. To prevent the unintentional release of these Wolbachia-infected females which might result in population replacement, a low dose of X-ray irradiation is deployed to sterilize any female escapees. However, it remains unclear whether these irradiation-induced male and female sterilizations share common mechanisms.
Advances and challenges in synthetic biology for mosquito control
28545Shih-Che Weng, Reem A. Masri, Omar S. Akbari, Trends in Parasitology, 2023-11-28 11:40:23.
Mosquito-borne illnesses represent a significant global health peril, resulting in approximately one million fatalities annually. West Nile, dengue, Zika, and malaria are continuously expanding their global reach, driven by factors that escalate mosquito populations and pathogen transmission. Innovative control measures are imperative to combat these catastrophic ailments. Conventional approaches, such as eliminating breeding sites and using insecticides, have been helpful, but they face challenges such as insecticide resistance and environmental harm. Given the mounting severity of mosquito-borne diseases, there is promise in exploring innovative approaches using synthetic biology to bolster mosquitoes' resistance to pathogens, or even eliminate the mosquito vectors, as a means of control. This review outlines current strategies, future goals, and the importance of gene editing for global health defenses against mosquito-borne diseases.
Scientific report urges debate on genetic modification to control insect pests
28490Bob Weber, CTV News, 2023-11-18 11:21:22.
Scientists are learning to turn the genetics of insect pests against themselves, altering the genome of familiar foes in ways that give farmers and doctors new ways to fight them. The burgeoning field offers fresh hope against old scourges such as malaria. And it could provide shiny new tools as familiar insecticides lose their punch and climate change shuffles the deck. But concerns buzz the new technology like a cloud of gnats. "Genetic pest-control tools could dramatically shift our relationship with the environment, not only because of their potential impact on the ecosystem of which we are a part, but also because of their challenge to the social and cultural values that shape decisions surrounding their use," says a new report from the Council of Canadian Academies.
Aedes aegypti microbiome composition covaries with the density of Wolbachia infection
28495Jane Pascar, Henry Middleton & Steve Dorus, Microbiome, 11. 2023-11-17 12:21:31.
Wolbachia is a widespread bacterial endosymbiont that can inhibit vector competency when stably transinfected into the mosquito, Aedes aegypti, a primary vector of the dengue virus (DENV) and other arboviruses. Although a complete mechanistic understanding of pathogen blocking is lacking, it is likely to involve host immunity induction and resource competition between Wolbachia and DENV, both of which may be impacted by microbiome composition. The potential impact of Wolbachia transinfection on host fitness is also of importance given the widespread release of mosquitos infected with the Drosophila melanogaster strain of Wolbachia (wMel) in wild populations. Here, population-level genomic data from Ae. aegypti was surveyed to establish the relationship between the density of wMel infection and the composition of the host microbiome.
The suppression of a selfish genetic element increases a male’s mating success in a fly
28422Sophie Lyth, Andrea J. Betancourt, Tom A. R. Price, Rudi L. Verspoor, Ecology and Evolution, 2023-11-12 13:33:47.
X chromosome meiotic drive (XCMD) kills Y-bearing sperm during spermatogenesis, leading to the biased transmission of the selfish X chromosome. Despite this strong transmission, some natural XCMD systems remain at low and stable frequencies, rather than rapidly spreading through populations. The reason may be that male carriers can have reduced fitness, as they lose half of their sperm, only produce daughters, and may carry deleterious alleles associated with XCMD. Thus, females may benefit from avoiding mating with male carriers, yielding a further reduction in fitness. Genetic suppressors of XCMD, which block the killing of Y sperm and restore fair Mendelian inheritance, are also common and could prevent the spread of XCMD. However, whether suppressed males are as fit as a wild-type male remains an open question, as the effect that genetic suppressors may have on a male's mating success is rarely considered. Here, we investigate the mating ability of XCMD males and suppressed XCMD males in comparison to wild-type males in the fruit fly Drosophila subobscura, where drive remains at a stable frequency of 20% in wild populations where it occurs. We use both competitive and non-competitive mating trials to evaluate male mating success in this system. We found no evidence that unsuppressed XCMD males were discriminated against. Remarkably, however, their suppressed XCMD counterparts had a higher male mating success compared to wild-type controls. Unsuppressed XCMD males suffered 12% lower offspring production in comparison to wild-type males. This cost appears too weak to counter the transmission advantage of XCMD, and thus the factors preventing the spread of XCMD remain unclear.
What are gene drives?
28374Anonymous, MalariaGEN, 2023-11-09 09:43:47.
Among the new generation of technological tools being developed to combat malaria, there is a lot of buzz around gene drives. This is a method for genetically modifying malaria-spreading mosquitoes and ultimately reducing or replacing their populations. But how exactly do gene drives work? And how can genomic surveillance data produced by the MalariaGEN community help gene drive researchers achieve their goals safely and effectively?
Symbiotic Wolbachia in mosquitoes and its role in reducing the transmission of mosquito-borne diseases: updates and prospects
28311A. Minwuyelet, G. P. Petronio, D. Yewhalaw, A. Sciarretta, I. Magnifico, D. Nicolosi, R. Di Marco and G. Atenafu, Frontiers in Microbiology, 14. 2023-11-08 08:20:47.
Mosquito-borne diseases such as malaria, dengue fever, West Nile virus, chikungunya, Zika fever, and filariasis have the greatest health and economic impact. These mosquito-borne diseases are a major cause of morbidity and mortality in tropical and sub-tropical areas. Due to the lack of effective vector containment strategies, the prevalence and severity of these diseases are increasing in endemic regions. Nowadays, mosquito infection by the endosymbiotic Wolbachia represents a promising new bio-control strategy. Wild-infected mosquitoes had been developing cytoplasmic incompatibility (CI), phenotypic alterations, and nutrition competition with pathogens. These reduce adult vector lifespan, interfere with reproduction, inhibit other pathogen growth in the vector, and increase insecticide susceptibility of the vector. Wild, uninfected mosquitoes can also establish stable infections through trans-infection and have the advantage of adaptability through pathogen defense, thereby selectively infecting uninfected mosquitoes and spreading to the entire population. This review aimed to evaluate the role of the Wolbachia symbiont with the mosquitoes (Aedes, Anopheles, and Culex) in reducing mosquito-borne diseases. Global databases such as PubMed, Web of Sciences, Scopus, and pro-Quest were accessed to search for potentially relevant articles. We used keywords: Wolbachia, Anopheles, Aedes, Culex, and mosquito were used alone or in combination during the literature search. Data were extracted from 56 articles’ texts, figures, and tables of the included article.
Biotechnological Potential of Microorganisms for Mosquito Population Control and Reduction in Vector Competence
28272R. D. Katak, A. M. Cintra, B. C. Burini, O. Marinotti, J. A. Souza-Neto and E. M. Rocha, Insects, 14. 2023-10-30 07:59:35.
Mosquitoes transmit pathogens that cause human diseases such as malaria, dengue fever, chikungunya, yellow fever, Zika fever, and filariasis. Biotechnological approaches using microorganisms have a significant potential to control mosquito populations and reduce their vector competence, making them alternatives to synthetic insecticides. Ongoing research has identified many microorganisms that can be used effectively to control mosquito populations and disease transmission. However, the successful implementation of these newly proposed approaches requires a thorough understanding of the multipronged microorganism-mosquito-;pathogen-environment interactions. Although much has been achieved in discovering new entomopathogenic microorganisms, antipathogen compounds, and their mechanisms of action, only a few have been turned into viable products for mosquito control. There is a discrepancy between the number of microorganisms with the potential for the development of new insecticides and/or antipathogen products and the actual available products, highlighting the need for investments in the intersection of basic research and biotechnology.
Conceptual risk assessment of mosquito population modification gene-drive systems to control malaria transmission: preliminary hazards list workshops
28220A. Kormos, G. Dimopoulos, E. Bier, G. C. Lanzaro, J. M. Marshall and A. A. James, Frontiers in Bioengineering and Biotechnology, 11. 2023-10-26 14:54:57.
The field-testing and eventual adoption of genetically-engineered mosquitoes (GEMs) to control vector-borne pathogen transmission will require them meeting safety criteria specified by regulatory authorities in regions where the technology is being considered for use and other locales that might be impacted. Preliminary risk considerations by researchers and developers may be useful for planning the baseline data collection and field research used to address the anticipated safety concerns. Part of this process is to identify potential hazards (defined as the inherent ability of an entity to cause harm) and their harms, and then chart the pathways to harm and evaluate their probability as part of a risk assessment. The University of California Malaria Initiative (UCMI) participated in a series of workshops held to identify potential hazards specific to mosquito population modification strains carrying gene-drive systems coupled to anti-parasite effector genes and their use in a hypothetical island field trial. The hazards identified were placed within the broader context of previous efforts discussed in the scientific literature. Five risk areas were considered i) pathogens, infections and diseases, and the impacts of GEMs on human and animal health, ii) invasiveness and persistence of GEMs, and interactions of GEMs with target organisms, iii) interactions of GEMs with non-target organisms including horizontal gene transfer, iv) impacts of techniques used for the management of GEMs and v) evolutionary and stability considerations. A preliminary hazards list (PHL) was developed and is made available here. This PHL is useful for internal project risk evaluation and is available to regulators at prospective field sites. UCMI project scientists affirm that the subsequent processes associated with the comprehensive risk assessment for the application of this technology should be driven by the stakeholders at the proposed field site and areas that could be affected by this intervention strategy.
Wolbachia enhances the survival ofDrosophila infected with fungal pathogens
28218J. Perlmutter, I., A. Atadurdyyeva, M. Schedl, E. and R. Unckless, L., bioRxiv, 2023.09.30.560320. 2023-10-11 14:49:32.
Wolbachia bacteria of arthropods are at the forefront of basic and translational research on multipartite host-symbiont-pathogen interactions. These microbes are vertically inherited from mother to offspring via the cytoplasm. They are the most widespread endosymbionts on the planet due to their infamous ability to manipulate the reproduction of their hosts to spread themselves in a population, and to provide a variety of fitness benefits to their hosts. Importantly, some strains of Wolbachia can inhibit viral pathogenesis within and between arthropod hosts. Mosquitoes carrying the wMel Wolbachia strain of Drosophila melanogaster have a greatly reduced capacity to spread viruses like dengue and Zika to humans. Therefore, Wolbachia are the basis of several global vector control initiatives. While significant research efforts have focused on viruses, relatively little attention has been given to Wolbachia-fungal interactions despite the ubiquity of fungal entomopathogens in nature. Here, we demonstrate that Wolbachia increase the longevity of their Drosophila melanogaster hosts when challenged with a spectrum of yeast and filamentous fungal pathogens. We find that this pattern can vary based on host genotype, sex, and fungal species. Further, Wolbachia correlates with higher fertility and reduced pathogen titers during initial fungal infection, indicating a significant fitness benefit. This study demonstrates Wolbachia’s role in diverse fungal pathogen interactions and determines that the phenotype is broad, but with several variables that influence both the presence and strength of the phenotype. These results enhance our knowledge of the strategies Wolbachia uses that likely contribute to such a high global symbiont prevalence.Importance Wolbachia bacteria of arthropods are at the forefront of global initiatives to fight arthropod-borne viruses. Despite great success in using the symbiont to fight viruses, little research has focused on Wolbachia-fungal interactions. Here, we find that Wolbachia of Drosophila melanogaster, the same strain widely used in antiviral initiatives, can also increase the longevity of flies systemically infected with a panel of yeast and filamentous fungal pathogens. The symbiont also partially increases host fertility and reduces fungal titers during early infection, indicating a significant fitness benefit. This represents a major step forward in Wolbachia research since its pathogen blocking abilities can now be extended to a broad diversity of another major branch of microbial life. This discovery may inform basic research on pathogen blocking and has potential translational applications in areas including biocontrol in agriculture.Competing Interest StatementThe authors have declared no competing interest.
Effect of 2 sex-sorting time schedules on SIT facility management
28345M. Malfacini, A. Puggioli, F. Balestrino, M. Carrieri, M. L. Dindo and R. Bellini, Journal of Insect Science, 23:9. 2023-09-18 10:58:06.
Improvements are needed in mosquito mass-rearing to effectively implement the sterile insect technique (SIT). However, managing this technique is challenging and resource intensive. SIT relies on mass rearing, sterilization, and release of adult males to reduce field populations. Maintaining an acceptable level of female presence, who can transmit viruses through biting, is crucial. Females are also essential for facility sustainability. Sex sorting plays a vital role in the production process, and our current mechanical sorting approach aims to obtain a high number of adult males with minimal female contamination within 24 h of pupation. Utilizing protandry helps control female contamination. While the 24-h sorting period achieves desired contamination levels, it may not yield enough females to sustain breeding lines, leading to increased labor costs that impact project sustainability. By delaying the sorting procedure to 48 h, we obtained sufficient females to sustain breeding lines, achieving a balance between male production and female contamination using the automatic version of the Fay–Morlan device as the sorting tool.
MGDrivE 3: A decoupled vector-human framework for epidemiological simulation of mosquito genetic control tools and their surveillance
27894A. Mondal, C. H. M. Sanchez and J. M. Marshall, bioRxiv, 2023.09.09.556958. 2023-09-12 08:11:56.
We present MGDrivE 3 (Mosquito Gene Drive Explorer 3), a new version of a previously-developed framework, MGDrivE 2, that investigates the spatial population dynamics of mosquito genetic control systems and their epidemiological implications. The new framework incorporates three major developments: i) a decoupled sampling algorithm allowing the vector portion of the MGDrivE framework to be paired with a more detailed epidemiological framework, ii) a version of the Imperial College London malaria transmission model, which incorporates age structure, various forms of immunity, and human and vector interventions, and iii) a surveillance module that tracks mosquitoes captured by traps throughout the simulation. Example MGDrivE 3 simulations are presented demonstrating the application of the framework to a CRISPR-based homing gene drive linked to dual disease-refractory genes and their potential to interrupt local malaria transmission. Simulations are also presented demonstrating surveillance of such a system by a network of mosquito traps. MGDrivE 3 is freely available as an open-source R package on CRAN (https://cran.r-project.org/package=MGDrivE2) (version 2.1.0), and extensive examples and vignettes are provided.
Can Gene-Drives Combat Vector-Borne Diseases?
27636Anonymous, tomorrow.bio, 2023-08-18 07:40:46.
Scientists, technophiles, and the medical community are abuzz with a topic that sounds like science fiction: gene-drives. Given the growing fear of vector-borne diseases, wouldn’t it be marvelous if we could meddle with genetics to drive vectors like mosquitoes to extinction? Sounds too good to be true? Let’s dive into it! Understanding Gene-Drives To comprehend how gene-drives might revolutionize disease control, we first need to understand what they are. Think of gene-drives as inherently selfish genes that ensure their own propagation throughout a population, bypassing traditional inheritance rules of mother nature. Quite enjoyably sneaky, isn't it?
Malaria’s latest foe? Bacteria.
27592M. Coulson, Johns Hopkins, 2023-08-07 06:38:09.
In a new paper published in Science, Marcelo Jacobs-Lorena, PhD, professor emeritus in Molecular Microbiology and Immunology, and his colleagues, in collaboration with researchers at GSK Global Health Medicines R&D, show that a naturally occurring bacterium and a chemical it secretes inhibit the malaria parasite’s development in mosquitoes—meaning they can’t transmit the parasite to humans. The method has distinct advantages: It’s low-tech, easily reproducible, and uses no genetic modification techniques. And, Jacobs-Lorena says, it can work in perfect concert with existing effective control strategies.
Suppression Trial through an Integrated Vector Management of Aedes albopictus (Skuse) Based on the Sterile Insect Technique in a Non-Isolated Area in Spain
27563C. Tur, D. Almenar, M. Zacarés, S. Benlloch-Navarro, I. Pla and V. Dalmau, Insects, 14. 2023-08-03 07:16:56.
In recent years, Aedes albopictus (Skuse, 1984) has expanded its distribution globally due to its high ecological plasticity. This expansion has increased the population’s susceptibility to contracting diseases such as dengue, Zika, and chikungunya, among others, which are transmitted by this mosquito species. In the absence of effective control methods, the application of the sterile insect technique (SIT) is proposed as part of an integrated vector management (IVM) program. From 2007 to 2020, this strategy has been tested in a non-isolated mosquito population urban area of 45 ha, representative of the municipalities of the Valencian region (Spain). The population levels of adult females and eggs collected in the traps have been reduced by 70–80% compared to the control area, demonstrating its efficacy in reducing mosquito populations. This work analyzes the impact of the migration of the wild mosquito population from the peri-urban area to the urban core.
Unleashing the swarm: Battling the global mosquito menace and defending public health
26467J. Entine and S. Moxon, Genetic Literacy Project, 2023-07-05 07:47:22.
There is one solution embraced by global health experts that should be pursued aggressively, if with some caution. Scientists in real-world trials have altered the genomes of entire animal populations, including mosquitoes, to thwart the vectoring of diseases and control pests — an innovation called gene drives. Emerging gene drive technologies offer enormous potential and have already shown their value in test projects in many parts of the world. More recently, the application of CRISPR/Cas9 tools has dramatically accelerated their effectiveness. But implementation on a wider scale is progressing at a snail’s pace. Why? For the most part, it is restrained by controversy, misunderstanding and the political opposition of activist environmental groups in Europe and North America.
Draft environmental assessment released for using modified mosquitoes to save native birds on Kauaʻi
26244Anonymous, Big Island NOW, 2023-06-23 07:24:12.
Today, the draft environmental assessment was made public for the use of Wolbachia-based incompatible male mosquitoes on Kauaʻi to stop the spread of avian malaria that is decimating native forest bird populations. The public has 31 days — from June 23 until July 24 — to comment on the draft, which was released by the U.S. Fish and Wildlife Service and the State of Hawaiʻi Division of Forestry and Wildlife. Hawaiʻi’s forest birds are facing an extinction crisis, with avian malaria a major factor. It is transmitted by non-native mosquitoes and just a single bite from an infected mosquito can be deadly. Of Kauaʻi’s 16 native honeycreepers, 10 have gone extinct and three are listed under the Endangered Species Act as threatened or endangered.
Generation game: gene-edited mosquitos to fight malaria
25551J. Opara, Sci Dev Net, 2023-06-07 08:44:49.
Population-level changes in the genetic make-up of one of the world’s deadliest animals could provide a key in the fight against malaria, proponents of a radical new technology argue. So-called gene drive technology, where genetic changes are passed down through generations, could rein in mosquito populations, or prevent them from passing on malaria.“Through genetic engineering, researchers have modified mosquitoes to favour the inheritance of genes that either will reduce the size of the population of those mosquitoes or stop them from transmitting the malaria parasite,” Michael Santos, senior vice-president and chief population health sciences officer at the US-based charity the Foundation for the National Institutes of Health (FNIH), tells SciDev.Net. “In other words, [it is about] using mosquitoes to control mosquitoes.” Malaria is one of the world’s “big three” deadly diseases, killing over half a million people in 2021, the vast majority in Africa.
Holobiont perspectives on tripartite interactions among microbiota, mosquitoes, and pathogens
25208R. Zheng, Q. Wang, R. Wu, P. N. Paradkar, A. A. Hoffmann and G. H. Wang, ISME, 2023-05-25 13:32:28.
Mosquito-borne diseases like dengue and malaria cause a significant global health burden. Unfortunately, current insecticides and environmental control strategies aimed at the vectors of these diseases are only moderately effective in decreasing disease burden. Understanding and manipulating the interaction between the mosquito holobiont (i.e., mosquitoes and their resident microbiota) and the pathogens transmitted by these mosquitoes to humans and animals could help in developing new disease control strategies. Different microorganisms found in the mosquito's microbiota affect traits related to mosquito survival, development, and reproduction. Here, we review the physiological effects of essential microbes on their mosquito hosts; the interactions between the mosquito holobiont and mosquito-borne pathogen (MBP) infections, including microbiota-induced host immune activation and Wolbachia-mediated pathogen blocking (PB); and the effects of environmental factors and host regulation on the composition of the microbiota. Finally, we briefly overview future directions in holobiont studies, and how these may lead to new effective control strategies against mosquitoes and their transmitted diseases.
Mosquito gene targeted RNAi studies for vector control
25650M. Yadav, N. Dahiya and N. Sehrawat, Functional and Integrative Genomics, 23:180. 2023-05-25 07:55:21.
Vector-borne diseases are serious public health concern. Mosquito is one of the major vectors responsible for the transmission of a number of diseases like malaria, Zika, chikungunya, dengue, West Nile fever, Japanese encephalitis, St. Louis encephalitis, and yellow fever. Various strategies have been used for mosquito control, but the breeding potential of mosquitoes is such tremendous that most of the strategies failed to control the mosquito population. In 2020, outbreaks of dengue, yellow fever, and Japanese encephalitis have occurred worldwide. Continuous insecticide use resulted in strong resistance and disturbed the ecosystem. RNA interference is one of the strategies opted for mosquito control. There are a number of mosquito genes whose inhibition affected mosquito survival and reproduction. Such kind of genes could be used as bioinsecticides for vector control without disturbing the natural ecosystem. Several studies have targeted mosquito genes at different developmental stages by the RNAi mechanism and result in vector control. In the present review, we included RNAi studies conducted for vector control by targeting mosquito genes at different developmental stages using different delivery methods. The review could help the researcher to find out novel genes of mosquitoes for vector control.
The boundary problem: Defining and delineating the community in field trials with gene drive organisms
25098N. de Graeff, I. Pirson, R. van der Graaf, A. L. Bredenoord and K. R. Jongsma, Bioethics, 2023-05-03 10:11:03.
Despite widespread and worldwide efforts to eradicate vector-borne diseases such as malaria, these diseases continue to have an enormous negative impact on public health. For this reason, scientists are working on novel control strategies, such as gene drive technologies (GDTs). As GDT research advances, researchers are contemplating the potential next step of conducting field trials. An important point of discussion regarding these field trials relates to who should be informed, consulted, and involved in decision-making about their design and launch. It is generally argued that community members have a particularly strong claim to be engaged, and yet, disagreement and lack of clarity exist about how this "community" should be defined and delineated. In this paper, we shed light on this "boundary problem": the problem of determining how boundaries of inclusion and exclusion in (GDT) community engagement should be drawn. As our analysis demonstrates, the process of defining and delineating a community is itself normative. First, we explicate why it is important to define and delineate the community. Second, we demonstrate that different definitions of community are used and intermingled in the debate on GDTs, and argue in favor of distinguishing geographical, affected, cultural, and political communities. Finally, we propose initial guidance for deciding who should (not) be engaged in decision-making about GDT field trials, by arguing that the definition and delineation of the community should depend on the rationale for engagement and that the characteristics of the community itself can guide the effective design of community engagement strategies.
Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages
25086A. Simoni, R. D'Amato, C. Taxiarchi, M. Galardini, A. Trusso, R. Minuz, S. Gilli, A. Somerville, D. Shittu, A. Khalil, R. Galizi and R. Muller, Research Square, 2023-04-24 06:46:30.
CRISPR-based gene drives have the potential to spread within a population and are considered as promising vector control tools. A doublesex-targeting gene drive was shown effective to suppress laboratory populations in both small and large cages, and it is considered for field application. Challenges related to the field-use of gene drives and the evolving regulatory framework demand for systems able to modulate or revert the action of gene drives, as part of post-release risk-mitigation plans. We developed an improved AcrIIA4-based anti-drive strain and showed inhibition of gene drive spread, in complex feeding and reproductive behavioural conditions. A stochastic model predicted the experimentally-observed genotypes dynamics in overlapping generations in medium- and large-sized cages and further demonstrated the effectiveness of anti-drive in different release and fitness scenarios. This study provides a further validation for the use of anti-drive system in controlling the spread of gene drive in Anopheles under complex behavioural conditions.
Targeting Sex Determination to Suppress Mosquito Populations
24988L. Ming, P. K. Nikolay, S. Ruichen, Y. Ting, D. B. Elena, J. B. Daniel, A. Igor, M. S. C. Hector, Z. Yinpeng, A. D. Nicolas, M. L. YuMin, P. S. Matthew, M. Craig, M. M. John and S. A. Omar, bioRxiv, 2023.04.18.537404. 2023-04-20 14:45:03.
Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Aedes aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to control wild populations, safely curtailing disease transmission.Competing Interest StatementO.S.A. is a founder of Agragene, Inc. with equity interest. O.S.A., M.L., and N.P.K are founders of Synvect with equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. All remaining authors declare no competing interests.
Defining transformation events for gene drive in species complexes
25001J. B. Connolly, IOBC-WPRS Bulletin, 163:8-20. 2023-04-13 15:11:40.
Engineered gene drives (EGDs) that allow the super-Mendelian inheritance of genetic traits could one day be used to reduce the vectorial capacity of Anopheles species that transmit human malaria in Africa. Many Anopheles species belong to complexes of closely related sibling species that can produce fertile interspecific hybrid females. In cases where the genomic target locus of the EGD is conserved amongst sibling species from the same complex as the released target species, it would therefore be plausible that the EGD could be vertically transmitted from the target species to sibling species by interspecific mating. To differentiate genetically modified organisms, the term ‘transformation event’ is used, based on the specific genomic location of the transgenic construct, as a result of random genomic integration. In contrast, an EGD is generated via its precise and reproducible insertion in its specific genomic target locus. These considerations pose two key questions for the use of EGD in species complexes: (i) what does the definition of “transformation event” mean in the context of vertical gene drive transfer of the EGD to sibling species in species complexes and (ii) does de novo transformation of an EGD into a sibling species constitute the same transformation event as introgression by backcrossing into a sibling species of an EGD that had been originally transformed in the target species? While definitions of the term transformation event that have been provided by national and intergovernmental organisations are somewhat ambiguous, they do provide scope for broad interpretation of vertical gene drive transfer of a specific EGD to different sibling species of the target species as the same transformation event. There also appears to be some consensus that definitions of transformation event support the notion that de novo transformations of an EGD in sibling species constitute the same transformation events as introgression by backcrossing into sibling species of an EGD that had been originally inserted in the target species.
In The Face Of Nigerian Mosquito Nets, Westerners’ Gene Editing Offers Hope
24964O. Onwumere, The Nigerian Voice, 2023-04-10 10:42:21.
In Nigeria, the utilization of mosquito nets is prevalent, while in the Western world, optimism is associated with the implementation of gene editing technology. In this article, ODIMEGWU ONWUMERE reports that malaria could soon be eradicated in Nigeria. According to US scientists, Anopheles mosquitoes have been genetically modified to resist the malaria-causing parasite by incorporating various anti-malaria molecules that target different stages of the parasite's lifecycle. Nevertheless, the article highlights a lack of information on the knowledge and overall viewpoint of Nigerian scientists concerning GMMs
A bacterium against the tiger: further evidence of the potential of non-inundative releases of males with manipulated Wolbachia infection in reducing fertility of Aedes albopictus field populations in Italy
24966B. Caputo, R. Moretti, C. Virgillito, M. Manica, E. Lampazzi, G. Lombardi, P. Serini, V. Pichler, N. W. Beebe, A. Della Torre and M. Calvitti, Pest Management Science, 2023-04-06 10:42:30.
BACKGROUND: Incompatible Insect Technique (IIT) is a population suppression approach based on the release of males with manipulated Wolbachia infection inducing egg inviability in wild females. We here present results of multiple field releases of incompatible ARwP males carried out in 2019 in a 2.7-ha green area within urban Rome (Italy) to assess the effect on Ae. albopictus egg viability. Data are compared with results obtained in 2018, when the approach was tested for the first time in Europe. RESULTS: An average of 4,674 ARwP males were released weekly for 7 weeks, resulting in a mean ARwP/wild male ratio of 1.1:1 (versus 0.7:1 in 2018). Egg-viability dynamics in ovitraps significantly varied between Treated and Control Sites, with an estimated overall reduction of 35% (versus 15% in 2018). The estimated proportion of females classified as mated with ARwP males was 41.8% and the viability rate of eggs laid by these females (9.5%) was on average significantly lower than that of females only mated with wild males (87.8%); however, high variability in fertility was observed. Values of ARwP male competitiveness were 0.36 and 0.73 based on the overall viability rate of eggs in ovitraps and on female fertility, respectively, i.e. well above the conventional 0.2 threshold for an effective suppressive impact in the field. CONCLUSIONS: Results further support the potential of IIT as a tool to contribute to Ae. albopictus control in the urban context, stressing the need of larger field trials to evaluate the cost-efficacy of the approach in temperate regions.
Regulatory and policy considerations for the implementation of gene drive-modified mosquitoes to prevent malaria transmission
24859S. L. James, B. Dass and H. Quemada, Transgenic Research, 32:17. 2023-03-15 15:00:05.
Gene drive-modified mosquitoes (GDMMs) are being developed as possible new tools to prevent transmission of malaria and other mosquito-borne diseases. To date no GDMMs have yet undergone field testing. This early stage is an opportune time for developers, supporters, and possible users to begin to consider the potential regulatory requirements for eventual implementation of these technologies in national or regional public health programs, especially as some of the practical implications of these requirements may take considerable planning, time and coordination to address. Several currently unresolved regulatory questions pertinent to the implementation of GDMMs are examined, including: how the product will be defined; what the registration/approval process will be for placing new GDMM products on the market; how the potential for transboundary movement of GDMMs can be addressed; and what role might be played by existing multinational bodies and agreements in authorization decisions. Regulation and policies applied for registration of other genetically modified organisms or other living mosquito products are assessed for relevance to the use case of GDMMs to prevent malaria in Africa. Multiple national authorities are likely to be involved in decision-making, according to existing laws in place within each country for certain product classes. Requirements under the Cartagena Protocol on Biodiversity will be considered relevant in most countries, as may existing regulatory frameworks for conventional pesticide, medical, and biocontrol products. Experience suggests that standard regulatory processes, evidence requirements, and liability laws differ from country to country. Regional mechanisms will be useful to address some of the important challenges.
RNA interference is essential to modulating the pathogenesis of mosquito-borne viruses in the yellow fever mosquito Aedes aegypti
24948G. H. Samuel, T. Pohlenz, Y. Dong, N. Coskun, Z. N. Adelman, G. Dimopoulos and K. M. Myles, Proceedings of the National Academy of Sciences, 120:e2213701120. 2023-03-14 10:39:54.
While it has long been known that the transmission of mosquito-borne viruses depends on the establishment of persistent and nonlethal infections in the invertebrate host, specific roles for the insects? antiviral immune pathways in modulating the pathogenesis of viral infections is the subject of speculation and debate. Here, we show that a loss-of-function mutation in the Aedes aegypti Dicer-2 (Dcr-2) gene renders the insect acutely susceptible to a disease phenotype upon infection with pathogens in multiple virus families associated with important human diseases. Additional interrogation of the disease phenotype demonstrated that the virus-induced pathology is controlled through a canonical RNA interference (RNAi) pathway, which functions as a resistance mechanism. These results suggest comparatively modest contributions of proposed tolerance mechanisms to the fitness of A. aegypti infected with these pathogens. Similarly, the production of virus-derived piwi-interacting RNAs (vpiRNAs) was not sufficient to prevent the pathology associated with viral infections in Dcr-2 null mutants, also suggesting a less critical, or potentially secondary, role for vpiRNAs in antiviral immunity. These findings have important implications for understanding the ecological and evolutionary interactions occurring between A. aegypti and the pathogens they transmit to human and animal hosts.
First report of natural Wolbachia infections in mosquitoes from Cuba
24933A. Ruiz, G. Gutiérrez-Bugallo, R. Rodríguez-Roche, L. Pérez, R. González-Broche, L. A. Piedra, L. C. Martínez, Z. Menéndez, A. Vega-Rúa and J. A. Bisset, Acta Tropica, 242:106891. 2023-03-11 08:20:20.
Mosquitoes are extensively responsible for the transmission of pathogens. Novel strategies using Wolbachia could transform that scenario, since these bacteria manipulate mosquito reproduction, and can confer a pathogen transmission-blocking phenotype in culicids. Here, we screened the Wolbachia surface protein region by PCR in eight Cuban mosquito species. We confirmed the natural infections by sequencing and assessed the phylogenetic relationships among the Wolbachia strains detected. We identified four Wolbachia hosts: Aedes albopictus, Culex quinquefasciatus, Mansonia titillans, and Aedes mediovittatus (first report worldwide). Knowledge of Wolbachia strains and their natural hosts is essential for future operationalization of this vector control strategy in Cuba.
A mosquito population suppression model with a saturated Wolbachia release strategy in seasonal succession
24814Z. Zhang, L. Chang, Q. Huang, R. Yan and B. Zheng, J Math Biol, 86:51. 2023-03-06 08:55:06.
Releasing Wolbachia-infected male mosquitoes to suppress wild female mosquitoes through cytoplasmic incompatibility has shown great promise in controlling and preventing mosquito-borne diseases. To make the release logistically and economically feasible, we propose a saturated release strategy, which is only implemented during the epidemic season of mosquito-borne diseases. Under this assumption, the model becomes a seasonally switching ordinary differential equation model. The seasonal switch brings rich dynamics, including the existence of a unique periodic solution or exactly two periodic solutions, which are proved by using the qualitative property of the Poincaré map. Sufficient conditions are also obtained for determining the stability of the periodic solutions.
Alleviating the burden of malaria with gene drive technologies? A biocentric analysis of the moral permissibility of modifying malaria mosquitoes
24800N. de Graeff, K. R. Jongsma and A. L. Bredenoord, Journal of Medical Ethics, 2023-02-28 08:33:28.
Gene drive technologies (GDTs) have been proposed as a potential new way to alleviate the burden of malaria, yet have also raised ethical questions. A central ethical question regarding GDTs relates to whether it is morally permissible to intentionally modify or eradicate mosquitoes in this way and how the inherent worth of humans and non-human organisms should be factored into determining this. Existing analyses of this matter have thus far generally relied on anthropocentric and zoocentric perspectives and rejected an individualist biocentric outlook in which all living organisms are taken to matter morally for their own sake. In this paper, we reconsider the implications of taking a biocentric approach and highlight nuances that may not be evident at first glance. First, we shortly discuss biocentric perspectives in general, and then outline Paul Taylor's biocentric theory of respect for nature. Second, we explore how conflicting claims towards different organisms should be prioritised from this perspective and subsequently apply this to the context of malaria control using GDTs. Our ethical analysis shows that this context invokes the principle of self-defence, which could override the pro tanto concerns that a biocentrist would have against modifying malaria mosquitoes in this way if certain conditions are met. At the same time, the case study of GDTs underlines the relevance of previously posed questions and criticism regarding the internal consistency of Taylor's egalitarian biocentrism.
Wolbachia RNase HI contributes to virus blocking in the mosquito Aedes aegypti
24468M. Hussain, G. Zhang, M. Leitner, L. M. Hedges and S. Asgari, iScience, 26:105836. 2023-01-15 08:41:00.
The endosymbiotic bacterium Wolbachia pipientis blocks replication of several arboviruses in transinfected Aedes aegypti mosquitoes. However, the mechanism of virus blocking remains poorly understood. Here, we characterized an RNase HI gene from Wolbachia, which is rapidly induced in response to dengue virus (DENV) infection. Knocking down w RNase HI using antisense RNA in Wolbachia-transinfected mosquito cell lines and A. aegypti mosquitoes led to increased DENV replication. Furthermore, overexpression of wRNase HI, in the absence of Wolbachia, led to reduced replication of a positive sense RNA virus, but had no effect on a negative sense RNA virus, a familiar scenario in Wolbachia-infected cells. Altogether, our results provide compelling evidence for the missing link between early Wolbachia-mediated virus blocking and degradation of viral RNA. These findings and the successful pioneered knockdown of Wolbachia genes using antisense RNA in cell line and mosquitoes enable new ways to manipulate and study the complex endosymbiont-host interactions.
East Maui project hopes mosquito v. mosquito mating battle will save endangered birds
24173K. Cerizo, MAUINOW, 2022-12-11 11:03:34.
A comprehensive overview of the existing microbial symbionts in mosquito vectors: An important tool for impairing pathogentransmission
24088V. Vandana, M. P. Kona, J. Kumar, O. P. Singh and K. C. Pandey, Experimental Parasitology, 243. 2022-11-30 09:06:12.
The emergence of drug-resistant parasites and/or insecticide-resistant mosquito vectors necessitates developing alternative tools that either supplement or replace the conventional malaria control strategies. Trans-infecting the mosquito vector with symbionts that can either compete with a targeted pathogen or manipulate the host biology by reducing its vectorial capacity could be a promising and innovative biological approach for the control of infectious diseases This idea could be utilized to develop a novel and efficient vector control strategy; symbionts are dispersed into vector populations to reduce their ability to transmit human pathogens. Here, we reported the natural existence of Microsporidian (an obligate fungus) in the field-collected An. stephensi mosquito. However, laboratory-reared An. stephensi and An. culicifacies did not exhibit microsporidian infection. Similarly, 16s rRNA PCR identified -1kb amplicons in laboratory-reared An. stephensi and An. culicifacies, indicating the presence of naturally residing different bacterial species. DNA sequencing of these amplicons revealed the identities of different bacteria which are not well-characterized in terms of plasmodia-interaction activity in the Indian malaria vector. This article summarizes an overview of the previously studied microbial symbionts for their role in Plasmodium transmission along with a list of new or unexplored symbionts in the disease transmitting mosquito vectors. The summarized information could be utilized to explore such microbial symbionts for their role in Plasmodium-transmission biology in-depth and implementation in the malaria control interventions globally.
Expression of mosquito miRNAs in entomopathogenic fungus induces pathogen-mediated host RNA interference and increases fungal efficacy
23853C. Cui, Y. Wang, Y. Li, P. Sun, J. Jiang, H. Zhou, J. Liu and S. Wang, Cell Reports, 41:111527. 2022-10-25 10:15:50.
Summary The growing threat of insecticide resistance prompts the urgent need to develop additional tools for mosquito control. Entomopathogenic fungi provide an eco-friendly alternative to chemical insecticides. One limitation to the use of mycoinsecticides is their relatively low virulence. Here, we report an approach for suppressing mosquito immunity and increasing fungal virulence. We engineered Beauveria bassiana to express Aedes immunosuppressive microRNAs (miRNAs) to induce host RNA interference (RNAi) immune responses. We show that engineered strains can produce and deliver the miRNAs into host cells to activate cross-kingdom RNAi during infection and suppress mosquito immunity by targeting multiple host genes, thereby dramatically increasing fungal virulence against Aedes aegypti and Galleria mellonella larvae. Importantly, expressing host miRNAs also significantly increases fungal virulence against insecticide-resistant mosquitoes, creating potential for insecticide-resistance management. This pathogen-mediated RNAi (pmRNAi)-based approach provides an innovative strategy to enhance the efficacy of fungal insecticides and eliminate the likelihood of resistance development.
Cross-kingdom RNAi to enhance the efficacy of insect pathogens
23851S. Asgari, Trends in Parasitology, 2022-10-25 10:11:07.
Insect pathogens play significant roles in the biocontrol of medical and agricultural pests. Cui et al. demonstrated that genetically modified (GM) fungi expressing host mosquito miRNAs could enhance the efficacy of the fungus by suppressing the host immune response. This opens avenues for utilisation of cross-kingdom RNAi in biocontrol.
Justifying an Intentional Species Extinction: The Case of Anopheles gambiae
23662D. E. Callies and Y. Rohwer, Environmental Values, 31:193-210. 2022-10-01 06:16:34.
Each year, over 200 million people are infected with the malaria parasite, nearly half a million of whom succumb to the disease. Emerging genetic technologies could, in theory, eliminate the burden of malaria throughout the world by intentionally eradicating the mosquitoes that transmit the disease. In this paper, we offer an ethical examination of the intentional eradication of Anopheles gambiae, the main malaria vector of sub-Saharan Africa. In our evaluation, we focus on two main considerations: the benefit of alleviating the malaria burden, and the loss of value that would accompany the eradication of the species. We outline a typology of the different ways in which species are valued or could be valuable, then use that typology to appraise the value of the species in question. We argue that Anopheles gambiae has minor (and redundant) instrumental value, little final subjective value and no objective final value.
How We’re Reducing Disease With Genetically Modified Mosquitoes
23667V. Wise, HealthMatch, 2022-09-29 08:07:21.
We all know mosquitoes as those annoying insects we swat away from our faces. They carry diseases, so we don’t want them anywhere near us. There are over 200 types of wild mosquitoes bugging us across America and the U.S. territories. Approximately 12 types can spread disease, but most are “nuisance” mosquitoes, which don’t spread germs. Obviously, it’s hard to identify a tiny flying creature, so we need to keep them all away from us just in case. Aedes aegypti¹ is one of the most common mosquitoes in the U.S. that can spread disease. One of the best-known mosquito-borne diseases is malaria, but Aedes aegypti is associated with 54 viruses². West Nile virus, Zika, and dengue are just three diseases these mosquitoes transmit around the U.S With 1 in 150 people becoming seriously ill due to West Nile virus, sometimes fatally, what can we do to prevent mosquito bites?
Can a bold new plan to stop mosquitoes catch on?
23631L. J. Young, Popular Science, 2022-09-13 07:48:42.
In the northwestern outskirts of Visalia in Tulare County, California, Bryan Ruiz drives down a familiar dirt road that cuts through farmland. He comes up to an irrigation pipe that’s created a “pretty nasty” situation—a small patch of vegetation and algae-covered water baking under the early June sun. As his shadow looms over the pool, a wormlike critter less than half an inch long quickly tries to submerge out of sight, but before it can, Ruiz scoops it up with a long metal dipper. He squints at his catch: a larva of Culex, a genus that includes common house mosquitoes.
Can mosquitoes be used for biological warfare?
23545Health Desk, Health Desk, 2022-09-07 06:05:21.
Every year, mosquitoes kill more people than any other creature in the world. Because of 1) mosquitoes’ ability to spread deadly, communicable diseases and cover large distances quickly, and 2) the fact that different types of bugs have been weaponized for hundreds of years, it is not surprising that mosquitoes have been used as weapons or suspected of being used as weapons. One of the most well known examples of mosquitoes being used as biological weapons occurred in the 20th century during World War II. Nazi researchers studied insects, including mosquitoes, to determine their ability to spread disease. The Nazi forces then went to Italian marshes to purposely collect mosquitoes with malaria and them into the population. While this is the most well-known case of using mosquitoes as biological warfare, the use or considered use of mosquitoes as weapons is not unique to Germany. For instance, Fort Detrick in Maryland was created during World War II to focus on defending the United States against biological weapons and researching biological weapons. One plan for the site in the late 1950s involved releasing mosquitoes infected with yellow fever virus against an enemy though this never actually happened.
Life-history traits of a fluorescent Anopheles arabiensis genetic sexing strain introgressed into South African genomic background
23550N. L. Ntoyi, T. Mashatola, J. Bouyer, C. Kraupa, H. Maiga, W. Mamai, N. S. Bimbile-Somda, T. Wallner, D. O. Carvalho, G. Munhenga and H. Yamada, Malaria Journal, 21:12. 2022-09-05 06:11:50.
Background South Africa has set a mandate to eliminate local malaria transmission by 2023. In pursuit of this objective a Sterile Insect Technique programme targeting the main vector Anopheles arabiensis is currently under development. Significant progress has been made towards operationalizing the technology. However, one of the main limitations being faced is the absence of an efficient genetic sexing system. This study is an assessment of an An. arabiensis (AY-2) strain carrying the full Y chromosome from Anopheles gambiae, including a transgenic red fluorescent marker, being introgressed into a South African genetic background as a potential tool for a reliable sexing system. Methods Adult, virgin males from the An. arabiensis AY-2 strain were outcrossed to virgin females from the South African, Kwazulu-Natal An. arabiensis (KWAG strain) over three generations. Anopheles arabiensis AY-2 fluorescent males were sorted as first instar larvae (L1) using the Complex Object Parametric Analyzer and Sorter (COPAS) and later screened as pupae to verify the sex. Life history traits of the novel hybrid KWAG-AY2 strain were compared to the original fluorescent AY-2 strain, the South African wild-type KWAG strain and a standard laboratory An. arabiensis (Dongola reference strain). Results The genetic stability of the sex-linked fluorescent marker and the integrity and high level of sexing efficiency of the system were confirmed. No recombination events in respect to the fluorescent marker were detected over three rounds of introgression crosses. KWAG-AY2 had higher hatch rates and survival of L1 to pupae and L1 to adult than the founding strains. AY-2 showed faster development time of immature stages and larger adult body size, but lower larval survival rates. Adult KWAG males had significantly higher survival rates. There was no significant difference between the strains in fecundity and proportion of males. KWAG-AY2 males performed better than reference strains in flight ability tests. Conclusion The life history traits of KWAG-AY2, its rearing efficiency under laboratory conditions, the preservation of the sex-linked fluorescence and perfect sexing efficiency after three rounds of introgression crosses, indicate that it has potential for mass rearing. The potential risks and benefits associated to the use of this strain within the Sterile Insect Technique programme in South Africa are discussed.
An evaluation of fusion partner proteins for paratransgenesis in Asaia bogorensis
24274C. Grogan, M. Bennett and D. J. Lampe, Plos One, 17:18. 2022-09-01 14:11:14.
Mosquitoes transmit many pathogens responsible for human diseases, such as malaria which is caused by parasites in the genus Plasmodium. Current strategies to control vector-transmitted diseases are increasingly undermined by mosquito and pathogen resistance, so additional methods of control are required. Paratransgenesis is a method whereby symbiotic bacteria are genetically modified to affect the mosquito's phenotype by engineering them to deliver effector molecules into the midgut to kill parasites. One paratransgenesis candidate is Asaia bogorensis, a Gram-negative bacterium colonizing the midgut, ovaries, and salivary glands of Anopheles sp. mosquitoes. Previously, engineered Asaia strains using native signals to drive the release of the antimicrobial peptide, scorpine, fused to alkaline phosphatase were successful in significantly suppressing the number of oocysts formed after a blood meal containing P. berghei. However, these strains saw high fitness costs associated with the production of the recombinant protein. Here, we report evaluation of five different partner proteins fused to scorpine that were evaluated for effects on the growth and fitness of the transgenic bacteria. Three of the new partner proteins resulted in significant levels of protein released from the Asaia bacterium while also significantly reducing the prevalence of mosquitoes infected with P. berghei. Two partners performed as well as the previously tested Asaia strain that used alkaline phosphatase in the fitness analyses, but neither exceeded it. It may be that there is a maximum level of fitness and parasite inhibition that can be achieved with scorpine being driven constitutively, and that use of a Plasmodium specific effector molecule in place of scorpine would help to mitigate the stress on the symbionts.
Release the Beast? Genetically modified mosquitos for diease control
23351G. Ferrante, Palatinate, 2022-07-29 08:31:10.
The company Oxitec is an example how genetic technologies can be used in managing unwanted species in a sustainable way.Oxitec jumped to the headlines in March with permits being issued by the United States Environmental Protection Agency (EPA) to allow the release of around 2.4 billion male mosquitos over two years in Florida and California. This is part of an expansion of their existing trial of releasing a genetically modified mosquito species in a bid to suppress the species Aedes aegypti in the USA. Aedes aegypti also known as the yellow fever mosquito has a main role in spreading debilitating diseases such as Dengue, Chikungunya, Yellow Fever and Zika virus in many countries. Aedes aegypti also is an invasive species in many subtropical regions, spanning from the south-eastern US to the Pacific Islands and South-East Asia. Oxitec’s signature technology involves the use of a ‘self-limiting’ gene which only activates in female mosquitos after reproduction.
Larval mosquito management and risk to aquatic ecosystems: A comparative approach including current tactics and gene-drive Anopheles techniques
23152R. K. D. Peterson and M. G. Rolston, Transgenic Research, 2022-07-07 09:39:09.
Genetic engineering of mosquitoes represents a promising tactic for reducing human suffering from malaria. Gene-drive techniques being developed that suppress or modify populations of Anopheles gambiae have the potential to be used with, or even possibly obviate, microbial and synthetic insecticides. However, these techniques are new and therefore there is attendant concern and uncertainty from regulators, policymakers, and the public about their environmental risks. Therefore, there is a need to assist decision-makers and public health stewards by assessing the risks associated with these newer mosquito management tactics so the risks can be compared as a basis for informed decision making. Previously, the effect of gene-drive mosquitoes on water quality in Africa was identified as a concern by stakeholders. Here, we use a comparative risk assessment approach for the effect of gene-drive mosquitoes on water quality in Africa. We compare the use of existing larvicides and the proposed genetic techniques in aquatic environments. Based on our analysis, we conclude that the tactic of gene-drive Anopheles for malaria management is unlikely to result in risks to aquatic environments that exceed current tactics for larval mosquitoes. As such, these new techniques would likely comply with currently recommended safety standards.
Intron-derived small RNAs for silencing viral RNAs in mosquito cells
23054P. Y. L. Tng, L. Z. Carabajal Paladino, M. A. E. Anderson, Z. N. Adelman, R. Fragkoudis, R. Noad and L. Alphey, PLOS Neglected Tropical Diseases, 16:e0010548. 2022-06-23 15:14:23.
Aedes aegypti and Ae. albopictus are the main vectors of mosquito-borne viruses of medical and veterinary significance. Many of these viruses have RNA genomes. Exogenously provided, e.g. transgene encoded, small RNAs could be used to inhibit virus replication, breaking the transmission cycle. We tested, in Ae. aegypti and Ae. albopictus cell lines, reporter based strategies for assessing the ability of two types of small RNAs to inhibit a chikungunya virus (CHIKV) derived target. Both types of small RNAs use a Drosophila melanogasterpremiRNA-1 based hairpin for their expression, either with perfect base-pairing in the stem region (shRNA-like) or containing two mismatches (miRNA-like). The pre-miRNA-1 stem loop structure was encoded within an intron; this allows co-expression of one or more proteins, e.g. a fluorescent protein marker tracking the temporal and spatial expression of the small RNAs in vivo. Three reporter-based systems were used to assess the relative silencing efficiency of ten shRNA-like siRNAs and corresponding miRNA-like designs. Two systems used a luciferase reporter RNA with CHIKV RNA inserted either in the coding sequence or within the 3’ UTR. A third reporter used a CHIKV derived split replication system. All three reporters demonstrated that while silencing could be achieved with both miRNA-like and shRNA-like designs, the latter were substantially more effective. Dcr-2 was required for the shRNA-like siRNAs as demonstrated by loss of inhibition of the reporters in Dcr-2 deficient cell lines. These positive results in cell culture are encouraging for the potential use of this pre-miRNA-1-based system in transgenic mosquitoes.
Sexual transmission of Anopheles gambiae densovirus (AgDNV) leads to disseminated infection in mated females
23030K. L. Werling, R. M. Johnson, H. C. Metz and J. L. Rasgon, Parasites and Vectors, 15:219. 2022-06-20 07:20:44.
Anopheles gambiae densovirus (AgDNV) is an insect-specific, single-stranded DNA virus that infects An. gambiae sensu stricto (s.s.), the major mosquito species responsible for transmitting malaria parasites throughout sub-Saharan Africa. AgDNV is a benign virus that is very specific to its mosquito host and therefore has the potential to serve as a vector control tool via paratransgenesis (genetic modification of mosquito symbionts) to limit transmission of human pathogens. Prior to being engineered into a control tool, the natural transmission dynamics of AgDNV between An. gambiae mosquitoes needs to be fully understood. Additionally, improved knowledge of AgDNV infection in male mosquitoes is needed. In the study presented here, we examined the tissue tropism of AgDNV in the male reproductive tract and investigated both venereal and vertical transmission dynamics of the virus.
Gene Drives: A Potentially New Weapon Against Mosquitoes
22905M. Sherman, Times Union Online, 2022-06-13 06:36:32.
Scientists have studied gene drives for more than 50 years, and to most of us this has been a well-kept secret. The development of a powerful genome editing tool in 2012, CRISPR/Cas9,1 led to recent breakthroughs in gene drive research that built on that half century’s worth of knowledge, and stimulated new discussions of the potential applications and implications of gene drive technologies. Just prior to the beginning of this study and since the committee was first convened, scientists published four proofs of concept — one in yeast, one in fruit flies, and two in different species of mosquitoes — that demonstrate the successful development of gene drives in the laboratory, at least in these organisms.Proposed applications for gene-drive modified organisms for basic research, conservation, agriculture, public health and other purposes will likely continue to expand as gene editing tools become more refined. Gene-drive modified organisms are on the horizon. With mosquitoes, the gene drive interferes with the insect’s ability to reproduce. It wiped out captive populations in eight or 12 generations. The first experimental release could be rolled out in Burkina Faso, Mali, Ghana or Uganda.
Current Status of Mosquito Handling, Transporting and Releasing in Frame of the Sterile Insect Technique
22868J. Guo, X. Zheng, D. Zhang and Y. Wu, Insects, 13. 2022-06-10 07:44:12.
The sterile insect technique (SIT) and its related technologies are considered to be a powerful weapon for fighting against mosquitoes. As an important part of the area-wide integrated pest management (AW-IPM) programs, SIT can help reduce the use of chemical pesticides for mosquito control, and consequently, the occurrence of insecticide resistance. The mosquito SIT involves several important steps, including mass rearing, sex separation, irradiation, packing, transportation, release and monitoring. To enable the application of SIT against mosquitoes to reduce vector populations, the Joint Food and Agriculture Organization of the United Nations (FAO) and the International Atomic Energy Agency (IAEA) Centre (previously called Division) of Nuclear Techniques in Food and Agriculture (hereinafter called Joint FAO/IAEA Centre) and its Insects Pest Control sub-program promoted a coordinated research project (CRP) entitled “Mosquito handling, transport, release and male trapping methods” to enhance the success of SIT. This article summarizes the existing explorations that are critical to the handling and transporting of male mosquitoes, offers an overview of detailed steps in SIT and discusses new emerging methods for mosquito releases, covering most processes of SIT.
Wolbachia 16S rRNA haplotypes detected in wild Anopheles stephensi in eastern Ethiopia
22568E. Waymire, S. Duddu, S. Yared, D. Getachew, D. Dengela, S. R. Bordenstein, M. Balkew, S. Zohdy, S. R. Irish and T. E. Carter, Parasites and Vectors, 15:178. 2022-05-24 08:50:15.
About two out of three Ethiopians are at risk of malaria, a disease caused by the parasites Plasmodium falciparum and Plasmodium vivax. Anopheles stephensi, an invasive vector typically found in South Asia and the Middle East, was recently found to be distributed across eastern and central Ethiopia and is capable of transmitting both P. falciparum and P. vivax. The detection of this vector in the Horn of Africa (HOA) coupled with widespread insecticide resistance requires that new methods of vector control be investigated in order to control the spread of malaria. Wolbachia, a naturally occurring endosymbiotic bacterium of mosquitoes, has been identified as a potential vector control tool that can be explored for the control of malaria transmission. Wolbachia could be used to control the mosquito population through suppression or potentially decrease malaria transmission through population replacement. However, the presence of Wolbachia in wild An. stephensi in eastern Ethiopia is unknown. This study aimed to identify the presence and diversity of Wolbachia in An. stephensi across eastern Ethiopia.
Self-Deleting Genes Could Control Mosquitoes And Prevent Vector-Borne Diseases
22493A. Russell, Texas AM TODAY, 2022-05-11 07:33:02.
Texas A&M AgriLife Research scientists are testing a technology to make temporary genetic modifications in mosquitoes that self-delete over time. The mechanism to make temporary genetic changes could be important for scientists hoping to modify mosquitoes in ways that help manage populations and prevent vector-borne diseases like West Nile virus without permanently altering wild populations’ genetic makeup. An article detailing their test results is published in Proceedings of the National Academy of Sciences’ PNAS Nexus. The authors, Zach Adelman and Kevin Myles, both professors in the Texas A&M University College of Agriculture and Life Sciences Department of Entomology, describe a method for programming the removal of edited genes within populations of mosquitoes over multiple generations. The method is a first step toward building safeguards for genetic modifications developed to control populations of mosquitoes and the vector-borne diseases they carry. The idea is to test proposed changes without making the changes permanent and without the risk of transmitting them to wild populations, Adelman said.
Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models
22288Y. Liu, W. Teo, H. Yang and J. Champer, bioRxiv, 2022.05.08.491087. 2022-05-08 08:15:29.
Suppression gene drives are designed to bias their inheritance and increase in frequency in a population, disrupting an essential gene in the process. When the frequency is high enough, the population will be unable to reproduce above the replacement level and could be eliminated. CRISPR suppression drives based on the homing mechanism have already seen success in the laboratory, particularly in malaria mosquitoes. However, several models predict that the use of these drives in realistic populations with spatial structure may not achieve complete success. This is due to the ability of wild-type individuals to escape the drive and reach empty areas with reduced competition, allowing them to achieve high reproductive success and leading to extinction-recolonization cycles across the landscape. Here, we extend our continuous space gene drive framework to include two competing species or predator-prey species pairs. We find in both discrete-generation and mosquito-specific models that the presence of a competing species or predator can greatly facilitate drive-based suppression, even for drives with modest efficiency. However, the presence of a competing species also substantially increases the frequency of outcomes in which the drive is lost before suppression is achieved. These results are robust in models with seasonal population fluctuations. We also found that suppression can be somewhat more difficult if targeting a predator with strong predator-prey interactions. Our results illustrate the difficulty of predicting outcomes of interventions that could substantially affect the populations of interacting species in complex ecosystems. However, our results are also potentially promising for the prospects of less powerful gene drives in achieving successful elimination of target pest populations.Competing Interest StatementThe authors have declared no competing interest.
The fight against malaria
22445F. Ammache, Year 2049, 2022-05-06 08:51:20.
Malaria is a disease we’ve been dealing with for thousands of years. Traces of the malaria parasite have been found in the remains of Egyptian mummies. Hippocrates described the fevers caused by malaria in Ancient Greece. The mosquito-filled Pontine Marshes protected Ancient Rome from invaders. Back then, we thought the disease was caused by people breathing “bad air”, or “mal aria”. The relationship between mosquitoes and malaria was unknown. Plasmodium falciparum, the deadliest form of malaria, was introduced by a new breed of mosquitoes around the 5th century. Some historians speculate that P. falciparum played a key role in the fall of the Roman Empire. It wasn’t until 1897 that we understood that mosquitoes transmitted malaria. Sir Ronald Ross, a British doctor based in India, found the malaria parasite in the blood of Anopheles mosquitoes which proved a hypothesis that was first put forward by his predecessor Alphonse Laveran.
Self-eliminating genes tested on mosquitoes
21924A. Russell, AGRILIFE Today, 2022-04-27 09:13:46.
Texas A&M AgriLife Research scientists have tested a technology to make temporary genetic modifications in mosquitoes. The modifications self-delete over time. Texas A&M AgriLife Research scientists published an article detailing a mechanism to make temporary genetic alterations to mosquitoes. The mechanism to make temporary genetic changes could be important for scientists hoping to modify mosquitoes in ways that help manage populations and prevent vector-borne diseases like West Nile virus without permanently altering wild populations’ genetic makeup.
Genetically Modified Mosquitoes May Be Released in California, Experts Express Concern
21719Z. Papadakis, NEWSMAX, 2022-04-11 09:25:49.
Millions of genetically engineered mosquitos could soon be set loose in California in an effort to curb the disease-carrying Aedes aegypti mosquito population — but some experts are concerned that it could backfire. On March 7, Oxitec, a private company, obtained a permit from the U.S. Environmental Protection Agency to release its mosquitos in specific districts in Florida and California. The company reasoned that its genetically modified insects could help to save the world half of the world's population from the invasive Aedes aegypti mosquito which, according to Oxitec, increases the risk of transmission of dengue, chikungunya, Zika, yellow fever, and other diseases. "Given the growing health threat this mosquito poses across the U.S., we're working to make this technology available and accessible," Grey Frandsen, CEO of Oxitec, said in a statement. "These pilot programs, wherein we can demonstrate the technology's effectiveness in different climate settings, will play an important role in doing so. We look forward to getting to work this year."
Comparison of Ground Release and Drone-Mediated Aerial Release of Aedes aegypti Sterile Males in Southern Mexico: Efficacy and Challenges
21574C. F. Marina, P. Liedo, J. G. Bond, A. R. Osorio, J. Valle, R. Angulo-Kladt, Y. Gómez-Simuta, I. Fernández-Salas, A. Dor and T. Williams, Insects, 13. 2022-03-31 12:43:15.
Sterile males of Aedes aegypti were released once a week for 8 weeks to evaluate the dispersal efficiency of ground and aerial drone release methods in a rural village of 26 Ha in southern Mexico. Indoor and outdoor BG-Sentinel traps were placed in 13–16 houses distributed throughout the village. The BG traps were activated 48 h after the release of the sterile males and functioned for a 24 h period following each release. Over the 8-week period of simultaneous ground and aerial releases, an average of 85,117 ± 6457 sterile males/week were released at ground level and 86,724 ± 6474 sterile males/week were released using an aerial drone. The ground release method resulted in higher numbers of captured males (mean = 5.1 ± 1.4, range 1.1–15.7 sterile males/trap) compared with the aerial release method (mean = 2.6 ± 0.8, range 0.5–7.3 sterile males/trap) (p < 0.05). Similarly, the prevalence of traps that captured at least one sterile male was significantly higher for ground release compared to the aerial release method (p < 0.01). The lower numbers of sterile males captured in the aerial release method could be due to mortality or physical injury caused by the chilling process for immobilization, or the compaction of these insects during transport and release. However, aerial releases by a two-person team distributed insects over the entire village in just 20 min, compared to ~90 min of work for a five-person team during the ground release method. Ground release also resulted in higher aggregations of males and some villagers reported feeling discomfort from the presence of large numbers of mosquitoes in and around their houses. We conclude that modifications to the handling and transport of sterile males and the design of containers used to store males are required to avoid injury and to improve the efficiency of aerial releases for area-wide SIT-based population suppression programs targeted at mosquito vectors of human disease.
Gene drives and population persistence vs elimination: The impact of spatial structure and inbreeding at low density
20529P. J. Beaghton and A. Burt, Theoretical Population Biology, 2022-03-03 08:28:52.
Synthetic gene drive constructs are being developed to control disease vectors, invasive species, and other pest species. In a well-mixed random mating population a sufficiently strong gene drive is expected to eliminate a target population, but it is not clear whether the same is true when spatial processes play a role. In species with an appropriate biology it is possible that drive-induced reductions in density might lead to increased inbreeding, reducing the efficacy of drive, eventually leading to suppression rather than elimination, regardless of how strong the drive is. To investigate this question we analyse a series of explicitly solvable stochastic models considering a range of scenarios for the relative timing of mating, reproduction, and dispersal and analyse the impact of two different types of gene drive, a Driving Y chromosome and a homing construct targeting an essential gene. We find in all cases a sufficiently strong Driving Y will go to fixation and the population will be eliminated, except in the one life history scenario (reproduction and mating in patches followed by dispersal) where low density leads to increased inbreeding, in which case the population persists indefinitely, tending to either a stable equilibrium or a limit cycle. These dynamics arise because Driving Y males have reduced mating success, particularly at low densities, due to having fewer sisters to mate with. Increased inbreeding at low densities can also prevent a homing construct from eliminating a population. For both types of drive, if there is strong inbreeding depression, then the population cannot be rescued by inbreeding and it is eliminated. These results highlight the potentially critical role that low-density-induced inbreeding and inbreeding depression (and, by extension, other sources of Allee effects) can have on the eventual impact of a gene drive on a target population.
Should we kill every mosquito on Earth?
20519J. Phelan, LiveScience, 2022-02-28 08:05:44.
Before you grab that can of bug spray, know this: While some mosquitoes are dangerous to us, not all are. Even those that are sometimes harmful tend not to feed on humans, preferring honeydew, plant sap and nectar, according to Mosquito Joe, a mosquito control company. There are around 3,500 mosquito species, but "only around 100 will potentially bite and spread disease to humans," Steven Sinkins, a professor in microbiology and tropical medicine at the Centre for Virus Research at the University of Glasgow in Scotland, told Live Science in an email. For instance, Culiseta mosquitoes often bite humans, but are not known to carry any debilitating diseases, while Toxorhynchites, which are common the world over and tend to live in forests, prefer nectar sugars to blood, according to Entomology Today. Therefore, it probably wouldn't be necessary to get rid of every mosquito species. Instead, we could target the more problematic ones, such as Aedes aegypti, which carry diseases such as yellow fever and Zika. A. aegypti is now ubiquitous, but it wasn't always this way. The species first spread out of Africa during the slave trade between the 15th and 19th centuries, through trade with Asia in the 18th and 19th centuries, and via troop movements during World War II, according to the World Mosquito Program, a nonprofit based in Australia.
Increased biting rate and decreased Wolbachia density in irradiated Aedes mosquitoes
20487R. Moretti, E. Lampazzi, C. Damiani, G. Fabbri, G. Lombardi, C. Pioli, A. Desiderio, A. Serrao and M. Calvitti, Parasites and Vectors, 15:67. 2022-02-24 08:48:28.
Releasing considerable numbers of radiation-sterilized males is a promising strategy to suppress mosquito vectors. However, releases may also include small percentages of biting females, which translate to non-negligible numbers when releases are large. Currently, the effects of irradiation on host-seeking and host-biting behaviors have not been exhaustively investigated. Information is also lacking regarding the effects of sterilizing treatment on the endosymbiotic bacterium Wolbachia, which is known to affect the vector competence of infected mosquitos.
A UC malaria initiative program receives grant for work researching genetically engineered mosquitoes
20483S. Slater, The California Aggie, 2022-02-23 08:39:35.
Malaria, a mosquito-borne infectious disease, was discovered in 1880, and has remained widespread in tropical regions around the equator including parts of Africa, Asia and Latin America, resulting in thousands of deaths and a significant blow to economic development in these regions. Many of the attempted strategies to eliminate malaria in the past have planned to do so by eliminating mosquitoes entirely — but according to a recent press release, the Vector Genetics Laboratory (VGL) at UC Davis, in collaboration with a UC malaria initiative program that originally started at UC Irvine, and with the financial support of a $10.2 million grant from Open Philanthropy, is taking a different approach. “Mosquitoes are a part of the ecosystem,” Greg Lanzaro, project principal investigator and director at VGL, said. “Our strategy does not eliminate mosquitoes. The mosquitoes will still be there, they’ll just be incapable of transmitting malaria. In every sense these mosquitoes are normal mosquitoes, except for the fact that they can’t transmit malaria.” The idea is called a “population modification strategy,” Lanzaro said, explaining that groups at UC Irvine and Johns Hopkins University genetically engineered mosquitoes that are incapable of transmitting the malaria parasite. “The way that malaria is transmitted is that the mosquito bites a person who has malaria and it picks up the parasite in the blood that it feeds on,” Lanzaro said. “Then the parasite develops in the mosquito so that when the mosquito bites the next person, they spread the parasite. Our mosquitoes have been engineered with a couple of genes that kill the parasite inside of the mosquito, so they’re not able to transmit.”
Evaluation of anti-malaria potency of wild and genetically modified Enterobacter cloacae expressing effector proteins in Anopheles stephensi
20485H. Dehghan, S. H. Mosa-Kazemi, B. Yakhchali, N. Maleki-Ravasan, H. Vatandoost and M. A. Oshaghi, Parasites and Vectors, 15:63. 2022-02-19 08:43:23.
Malaria is one of the most lethal infectious diseases in tropical and subtropical areas of the world. Paratransgenesis using symbiotic bacteria offers a sustainable and environmentally friendly strategy to combat this disease. In the study reported here, we evaluated the disruption of malaria transmission in the Anopheles stephensi-Plasmodium berghei assemblage using the wild-type (WT) and three modified strains of the insect gut bacterium, Enterobacter cloacae.
Gene drive mosquitoes can aid malaria elimination by retarding Plasmodium sporogonic development
20447A. Hoermann, T. Habtewold, P. Selvaraj, G. Del Corsano, P. Capriotti, M. G. Inghilterra, K. M. Temesgen, G. K. Christophides and N. Windbichler, bioRxiv, 2022.02.15.480588. 2022-02-17 09:41:11.
Gene drives hold promise for the genetic control of malaria vectors. The development of vector population modification strategies hinges on the availability of effector mechanisms impeding parasite development in transgenic mosquitoes. We augmented a midgut gene of the malaria mosquito Anopheles gambiae to secrete two exogenous antimicrobial peptides, Magainin 2 and Melittin. This small genetic modification, capable of efficient non-autonomous gene drive, hampers oocyst development in both Plasmodium falciparum and Plasmodium berghei. It delays the release of infectious sporozoites while it simultaneously reduces the lifespan of homozygous female transgenic mosquitoes. Modeling the spread of this modification using a large-scale agent-based model of malaria epidemiology reveals that it can break the cycle of disease transmission across a range of endemic settings.Competing Interest StatementThe authors have declared no competing interest.
C-type lectin 4 regulates broad-spectrum melanization-based refractoriness to malaria parasites
20489M. L. Simões, Y. Dong, G. Mlambo and G. Dimopoulos, PLOS Biology, 20:e3001515. 2022-02-13 08:53:42.
Anopheles gambiae melanization-based refractoriness to the human malaria parasite Plasmodium falciparum has rarely been observed in either laboratory or natural conditions, in contrast to the rodent model malaria parasite Plasmodium berghei that can become completely melanized by a TEP1 complement-like system-dependent mechanism. Multiple studies have shown that the rodent parasite evades this defense by recruiting the C-type lectins CTL4 and CTLMA2, while permissiveness to the human malaria parasite was not affected by partial depletion of these factors by RNAi silencing. Using CRISPR/Cas9-based CTL4 knockout, we show that A. gambiae can mount melanization-based refractoriness to the human malaria parasite, which is independent of the TEP1 complement-like system and the major anti-Plasmodium immune pathway Imd. Our study indicates a hierarchical specificity in the control of Plasmodium melanization and proves CTL4 as an essential host factor for P. falciparum transmission and one of the most potent mosquito-encoded malaria transmission-blocking targets.
Quality Control Methods for Aedes albopictus Sterile Male Transportation
20392G. D. Mastronikolos, A. Kapranas, G. K. Balatsos, C. Ioannou, D. P. Papachristos, P. G. Milonas, A. Puggioli, I. Pajović, D. Petrić, R. Bellini, A. Michaelakis and N. T. Papadopoulos, Insects, 2022-02-09 09:27:23.
Genetic based mosquito control methods have been gaining ground in recent years for their potential to achieve effective suppression or replacement of vector populations without hampering environments or causing any public health risk. These methods require the mass rearing of the target species in large facilities sized to produce millions of sterile males, as already well established for a number of insects of agricultural importance. Assessing the performance of released males in Sterile Insect Technique (SIT) control programs is of the utmost importance for the success of the operation. Besides the negative effects of mass rearing and sterilization, the handling of sterilized insects and shipment to distant areas may also negatively impact the quality of sterilized males. The aim of the current study was to design and executive quality control (QC) tests for sterilized Aedes albopictus (Asian tiger mosquito) males delivered by air shipment from the mass production facility located in Italy to Greece and Montenegro field release sites. Mass reared mosquito strains were based on biological materials received from Italy, Greece and Montenegro. Tests conducted at the mass rearing facility before transportation revealed a rather high residual female contamination following mechanical sex separation (approximately 1.5% females, regardless of the mosquito strain). Irradiated males of all three mosquito strains induced high levels of sterility to females. Shipment lasting approximately 24 h resulted in approximately 15% mortality, while when shipment lasted nearly two days this increased to almost 40%. The flight ability of sterilized males following one day transportation time was satisfactory (over 60%). The response of sterile males to food and water starvation was comparable and slightly lower than that of wild non-transported males. Longevity of sterile males was shorter than that of wild counterparts and it seems it was not affected by mating to wild females. Both mating propensity and mating competitiveness for wild virgin females was higher for the wild, control males compared to the sterile, transported ones. Overall, the performance of sterile male Ae. albopictus delivered from the mass rearing facility of Italy to Greece in approximately 24 h was satisfactory. Transportation lasting two days or longer incurred detrimental effects on males, which called into question the outcome of the SIT release programs. In conclusion, our results demonstrate the need of quality control procedures, especially when sterile male production facilities are not near to the releasing point. Transportation could be a serious drawback for the implementation of Sterile Insect Releases and, consequently, it is important to establish an efficient and fast transportation of sterilized males in advance.
Could Crispr Flip the Switch on Insects’ Resistance to Pesticides?
20288E. Mullin, WIRED, 2022-02-02 11:53:17.
WHILE THE COVID-19 pandemic raged across the world in 2020, another disease was quietly infecting more than 220 million people on the continent of Africa: malaria. That year, the disease led to more than 600,000 deaths, most of them children. Caused by the parasite Plasmodium, the illness is spread through the bites of infected female Anopheles mosquitoes. Insecticide-treated bed nets and indoor spraying have long been some of the most effective strategies for combating the disease. But decades of using these chemicals has lessened their potency. It happens like this: Insecticides kill off most of the mosquitoes in an area. But a small number may survive because something about their genetic makeup makes them unaffected by the pesticide. Mosquitoes within that small population mate with each other and pass on their genes to their offspring, breeding more resistant mosquitoes. In some cases, resistance has built up just a few years after the introduction of an insecticide. It makes fighting deadly mosquitoes a constant game of whack-a-mole. Insecticides remain the frontline in fighting malaria, because interventions like building mosquito-resistant housing are still experimental, and the effort to develop a vaccine has taken decades. Last summer the World Health Organization recommended Mosquirix, the first anti-parasitic vaccine, for African children under age 5, but it is only 30 percent effective at preventing serious disease, and will take many years to achieve approval and distribution among individual nations.
Crisp Genes
20283J. Mckenna, The Simple Science, 2022-01-29 11:44:36.
Imagine we had the power to use genetic technologies to stop one of humanity’s most dangerous predators. What is that predator? Sharks? Crocodiles? Snakes? Think far, far smaller. It is in fact, the mosquito.Mosquitos cause all sorts of nasty diseases like the Zika Virus, Dengue Fever, Yellow Fever, and malaria. While nobody really wants to contract any of those diseases, and they’ll all make you pretty miserable, they’re nothing compared to the frankly hellacious malaria being one of the single biggest killers of humans in history. Well, plot twist, we actually do have the technology and it comes in the form of some genetic machinery discovered in bacteria: CRISPR-Cas9 (or CRISPR for short).
CRISPR Technology Can Eliminate Disease-Spreading Mosquitoes
20133S. Krishana, Now, 2022-01-19 13:10:41.
Scientists have uncovered a new technique they call the “precision-guided sterile insect technique,” or pgSIT. While most CRISPR procedures affect organisms that spread diseases by passing a gene change down generations, this system is more limited. It targets male mosquito genes that are linked to fertility. As a result of changing these genes, any offspring these mosquitoes have would be infertile. “pgSIT is a new scalable genetic control system that uses a CRISPR-based approach to engineer deployable mosquitoes that can suppress populations,” said Omar Akbari, one of the study’s authors. “Males don’t transmit diseases, so the idea is that, as you release more and more sterile males, you can suppress the population without relying on harmful chemicals and insecticides.” But it’s the female population that spreads diseases, so pgSIT targets them, as well. According to the study, the CRISPR technology treatment renders female mosquitoes unable to fly or hold their wings up. It also makes them slower and more lethargic in their movements. Combined, these effects lower the chances that these female mosquitoes will mate or successfully find a blood source and attach to it to spread disease.
Genetic Strategy Reverses Insecticide Resistance
20108H. Tasoff, The Current, 2022-01-18 17:08:09.
University of California biologists have now developed a method that reverses insecticide resistance using CRISPR/Cas9 technology. A team including UC Santa Barbara researchers Craig Montell(link is external) and Menglin Li(link is external), UC San Diego researchers Bhagyashree Kaduskar, Raja Kushwah and Professor Ethan Bier of UCSD’s Tata Institute for Genetics and Society (TIGS) used the genetic editing tool to replace an insecticide-resistant gene in fruit flies with the normal insecticide-susceptible form. Their achievement, described in Nature Communications(link is external), could significantly reduce the amount of insecticides used. “This strategy could be used to reverse the resistance of mosquito disease vectors that spread devastating diseases that impact hundreds of millions of people each year,” said Craig Montell, a professor of molecular, cellular and developmental Biology at UC Santa Barbara.
Nuclear technique cuts mosquito numbers in Cuban trial
20111M. A. Madsen, IAEA, 2022-01-13 17:14:31.
A pilot trial of a SIT campaign was conducted between April and August 2020 in an area of 50 hectares in El Cano, an isolated neighbourhood of southwest Havana. Arroyo Arenas, another neighbourhood of similar size, was used as an untreated control site. In the pilot trial, almost 1.3 million sterile male mosquitoes were released. Male mosquitos do not carry dengue, bite, nor feed on blood. The IAEA supported Cuba in attaining equipment to separate male and female mosquitoes ahead of irradiation and release and helped equip mosquito rearing facilities. Prior to the trial, Cuba had little capacity in insect rearing and the IAEA supported Cuban fellows to be sent for training on the technique in Brazil, Colombia, Mexico and at the IAEA laboratories in Austria. "Using the SIT for mosquitoes is relatively new anywhere in the world, and pilot trials like this one show how promising they can be," said Rui Cardoso Pereira, Head of the Insect Pest Control Section at the Joint FAO/IAEA Centre of Nuclear Techniques for Food and Agriculture.
Effects of Sterile Males and Fertility of Infected Mosquitoes on Mosquito-Borne Disease Dynamics
20097X. L. Sun, S. Q. Liu, Y. F. Lv and Y. Z. Pei, Bulletin of Mathematical Biology, 84:33. 2022-01-13 09:37:31.
By studying an infection-age structured model, we consider the effects of releasing sterile males and the fertility of infected mosquitoes on the mosquito-borne diseases transmission including the extinction of mosquitoes, the elimination and persistence of diseases. Firstly, equivalent integral equations are established to prove the well-posedness of solutions. Then, the main results of disease dynamics are given. By taking chikungunya as a numerical simulation example, an optimal releasing threshold is given according to our presupposed control standard. When the fertility disturbance of infected mosquitoes is small, the high releasing amount plays a main role on the control of the disease; however, when the fertility disturbance is large, the initial distributions and the fertility of infected mosquitoes are the key factors to control the disease. Mathematically, the fertility of infected mosquitoes makes the system have complex dynamics with multiple positive equilibria and bistability.
Reversing insecticide resistance with allelic-drive in Drosophila melanogaster
20085B. Kaduskar, R. B. S. Kushwah, A. Auradkar, A. Guichard, M. Li, J. B. Bennett, A. H. F. Julio, J. M. Marshall, C. Montell and E. Bier, Nature Communications, 13:291. 2022-01-12 09:16:33.
A recurring target-site mutation identified in various pests and disease vectors alters the voltage gated sodium channel (vgsc) gene (often referred to as knockdown resistance or kdr) to confer resistance to commonly used insecticides, pyrethroids and DDT. The ubiquity of kdr mutations poses a major global threat to the continued use of insecticides as a means for vector control. In this study, we generate common kdr mutations in isogenic laboratory Drosophila strains using CRISPR/Cas9 editing. We identify differential sensitivities to permethrin and DDT versus deltamethrin among these mutants as well as contrasting physiological consequences of two different kdr mutations. Importantly, we apply a CRISPR-based allelic-drive to replace a resistant kdr mutation with a susceptible wild-type counterpart in population cages. This successful proof-of-principle opens-up numerous possibilities including targeted reversion of insecticide-resistant populations to a native susceptible state or replacement of malaria transmitting mosquitoes with those bearing naturally occurring parasite resistant alleles.
The prince, the mayor, and the U.S. fish that ate Japan
20103C. Elliot, National Geographic, 2022-01-11 16:44:32.
When Crown Prince Akihito visited Chicago on October 3, 1960, his sole request was to visit Shedd Aquarium. Then Mayor Richard J. Daley, an avid angler, presented the prince with a gift that he scooped with a net from one of the tanks himself: 18 bluegills, the official Illinois state fish. The 26-year-old future emperor was already a passionate ichthyologist, and he planned to stock the exotic fish in the moat surrounding his palace, according to accounts in the Chicago Tribune at the time. At windy Chicago O’Hare International Airport the next day with Princess Michiko, Akihito bid the city farewell, carrying a gift that he couldn’t have imagined would cause a decades-long ecological crisis in his homeland. In the intervening six decades, the bluegills became an invasive, species-destroying nightmare, crowding Japanese freshwater lakes and rivers and destroying native fish biodiversity, says Kenji Saitoh, a researcher at the country’s Fisheries Resources and Education Agency. Fortunately, science has marched on in 60 years. Now, Japanese geneticists are experimenting with the gene editing wizardry of CRISPR to sterilize the invasive bluegills. If the initiative succeeds, wildlife managers could use the same technique to rid the U.S. of damaging aquatic invasives such as the Asian carp.
Introgression of the Aedes aegypti red-eye genetic sexing strains into different genomic backgrounds for sterile insect technique applications
20137A. A. Augustinos , K. Nikolouli , L. D. De La Fuente , M. Misbah-Ul-Haq, D. O. Carvalho and K. Bourtzis, Frontiers in Bioengineering and Biotechnology, 2022-01-11 13:16:31.
Aedes aegypti is an invasive mosquito species and major vector of human arboviruses. A wide variety of control methods have been employed to combat mosquito populations. One of them is the sterile insect technique (SIT) that has recently attracted considerable research efforts due to its proven record of success and the absence of harmful environmental footprints. The efficiency and cost-effectiveness of SIT is significantly enhanced by male-only releases. For mosquito SIT, male-only releases are ideally needed since females bite, blood-feed, and transmit the pathogens. Ae. aegypti genetic sexing strains (GSS) have recently become available and are based on eye color mutations that were chosen as selectable markers. These genetic sexing strains were developed through classical genetics and it was shown to be subjected to genetic recombination, a phenomenon that is not suppressed in males as is the case in many Diptera. The genetic stability of these GSS was strengthened by the induction and isolation of radiation-induced inversions. In this study, we used the red eye mutation and the inversion Inv35 line of the Ae. aegypti red-eye GSS s and introgressed them in six different genomic backgrounds to develop GSS with the respective local genomic backgrounds. Our goal was to assess whether the recombination frequencies in the strains with and without the inversion are affected by the different genomic backgrounds. In all cases the recombination events were suppressed in all Inv35 GSS strains, thus indicating that the genomic background does not negatively affect the inversion result. The absence of any effect that could be ascribed to genetic differences, enables the introgression of the key elements of the GSS into the local genomic background prior to release to the target areas. Maintaining the local background increases the chances for successful matings between released males and wild females and addresses potential regulatory concerns regarding biosafety and biosecurity.
Lab-scale characterization and semi-field trials of Wolbachia Strain wAlbB in a Taiwan Wolbachia introgressed Ae. aegypti strain
20383W. L. Liu, H. Y. Yu, Y. X. Chen, B. Y. Chen, S. N. Leaw, C. H. Lin, M. P. Su, L. S. Tsai, Y. Chen, S. H. Shiao, Z. Y. Xi, A. C. C. Jang and C. H. Chen, PLOS Neglected Tropical Diseases, 16:24. 2022-01-11 08:53:33.
Author summaryPrior to open field release, new genetic approaches that interfere with mosquito abilities and reduce mosquito population density require progressive evaluation both in the laboratory and contained field trials. Trials in contained outdoor systems are thus an important step and allow for evaluation of the effectiveness and reliability of Wolbachia-infected Aedes aegypti (wAlbB-Tw) in settings that incorporate natural environmental variations. We describe a semi-field system designed to study the ability of wAlbB-Tw mosquitoes to suppress local mosquito populations. We provide a protocol for establishing, maintaining, and monitoring Ae. aegypti population densities inside field cages. These results pave the way for the open release of wAlbB-Tw-infected Ae. aegypti mosquitoes in the field. Dengue fever is one of the most severe viral diseases transmitted by Aedes mosquitoes, with traditional approaches of disease control proving insufficient to prevent significant disease burden. Release of Wolbachia-transinfected mosquitoes offers a promising alternative control methodologies; Wolbachia-transinfected female Aedes aegypti demonstrate reduced dengue virus transmission, whilst Wolbachia-transinfected males cause zygotic lethality when crossed with uninfected females, providing a method for suppressing mosquito populations. Although highly promising, the delicate nature of population control strategies and differences between local species populations means that controlled releases of Wolbachia-transinfected mosquitoes cannot be performed without extensive testing on specific local Ae. aegypti populations. In order to investigate the potential for using Wolbachia to suppress local Ae. aegypti populations in Taiwan, we performed lab-based and semi-field fitness trials. We first transinfected the Wolbachia strain wAlbB into a local Ae. aegypti population (wAlbB-Tw) and found no significant changes in lifespan, fecundity and fertility when compared to controls. In the laboratory, we found that as the proportion of released male mosquitoes carrying Wolbachia was increased, population suppression could reach up to 100%. Equivalent experiments in semi-field experiments found suppression rates of up to 70%. The release of different ratios of wAlbB-Tw males in the semi-field system provided an estimate of the optimal size of male releases. Our results indicate that wAlbB-Tw has significant potential for use in vector control strategies aimed at Ae. aegypti population suppression in Taiwan. Open field release trials are now necessary to confirm that wAlbB-Tw mediated suppression is feasible in natural environments.
The Need for a Tiered Registry for US Gene Drive Governance
20003K. L. Warmbrod, A. L. Kobokovich, R. West, G. K. Gronvall and M. Montague, Health Security, 2022-01-10 10:08:26.
A great deal of attention has been focused on the potential risks of gene drives, the kinds of biosafety protections they may require, and how they may be reversed; however, less attention has been paid to the systems that would be useful to have in place in the future, when multiple gene drives may be fielded in multiple species, environments, and countries.4-7 The need for coordinated governance of these technologies will become more pressing as gene drive technologies advance and more drives are created to address other vector-borne diseases like the West Nile virus, agricultural pest management, or invasive species. Gene drives carry different inherent risks compared with other genetically modified organisms (GMOs). Existing governance mechanisms for traditional GMOs are insufficient for oversight of gene drives, which require different systems to assess their usefulness and safety. To address the needs for enhanced oversight, we propose a tiered registry system, similar to the clinical trials databases, which can provide government officials, researchers, biotechnology companies, and the public with useful information about ongoing gene drive research or previously released gene drives. Such a resource would enable scientists to confirm that new gene drives would not interfere with existing drives, provide the public with the information needed to make informed decisions concerning consent for release of gene drives, provide researchers with technical information needed to prevent collisions of independent projects modifying the same organism, and provide regulators with information critical for effective oversight. We propose that the US government should implement such a registry for gene drives in the United States, which does not have a robust gene drive regulatory system in place and is not party to the international treaty most relevant for international gene drive regulation, the Convention on Biological Diversity.8 In this commentary, we describe current efforts to safely regulate gene drive and similar genetic technologies worldwide and how the United States could build a tiered registry database that is specifically designed to regulate such technologies throughout a drive's life cycle.
Information Sharing in Senegal on the Gene Drive Technology as a potential Complementary Tool for Malaria Vector Control
19902AUDA-NEPAD, AUDA-NEPAD, 2022-01-04 08:23:49.
AUDA-NEPAD in partnership with the National Biosafety Authority (Autorité Nationale de Biosécurité (ANB) in Senegal organized an Information sharing meeting on the gene drive technology as a complementary tool for malaria vector control, from 22-23 December 2021, in Somone, Senegal. The key objective of the meeting was to discuss the opportunities offered by gene drive technology for malaria control, based on the current state of art of knowledge and experiences from countries that are testing this approach. Sixty people, including key stakeholders from relevant institutions in Senegal and experts from Burkina Faso and Mali took part in the meeting. In his opening remarks, Mr. Ousseynou Kassé, Executive Director of ANB thanked AUDA-NEPAD for the support provided in the organization of this meeting. He also thanked the experts from Burkina Faso and Mali who came to share their experiences on the subject. “We started the discussions on the Gene Drive approach some years ago at the COP-MOP meeting held in Mexico and we continued it in the past years in the sub-region. Recently we were in Accra twice to discuss the same topic ahead of the next COP-MOP meeting”, he said. Mr. Yero Dé, Chairperson of the Orientation Council of ANB, highlighted that the meeting seeks to improve stakeholders’ understanding of the gene drive technology as a novel malaria control approach. “We need to consider adopting this new approach through an open discussion on how this technology could be used in the health sector and in particular in malaria control and elimination. Malaria mortality rate is very high in most of our countries and the efforts deployed so far to control the disease face important challenges, including the resistance of the vector to the current treatments”, he further stated.
Driving the Self-Destruction of Malaria-Transmitting Mosquitos
19948H. Aliouche, News Medical Life Sciences, 2021-12-22 09:36:57.
Self-destruction of malaria-transmitting mosquitoes can be driven by gene drives deployed to manipulate natural populations. In particular, they can be used to reduce the number of individuals in a population or to modify their composition; this is particularly useful when such species are vectors of disease. The use of genetic engineering tools is becoming increasingly widespread and enables the deployment of natural and synthetic gene drivers that can propagate a particular subset of genetic expressions population through the biasing of Mendelian inheritance laws.
Temporal Viability of Aedes aegypti and Aedes albopictus Eggs Using Two Hygroscopic Substances as Preservatives under a Sterile Insect Technique (SIT) Program in Southern Mexico
19721E. N. Martínez-García, E. E. Díaz-González, C. F. Marina, J. G. Bond, J. J. Rodríguez-Rojas, G. Ponce-García, R. M. Sánchez-Casas and I. Fernández-Salas, Insects, 13. 2021-12-21 12:31:48.
Dengue and other Aedes-borne diseases have dramatically increased over the last decades. The Sterile Insect Technique (SIT) has been successfully used as part of integrated pest strategies to control populations of insect-plant and livestock pests and is currently being tested as a potential method to reduce mosquito populations in an environmentally friendly approach. However, during the mass rearing steps needed to produce millions of mosquitoes, egg storage and preservation are essential for a certain amount of time. Eggs of Aedes aegypti have a chorionic pad that functions as a sticky substance to glue them onto the inner walls of larval breeding sites. The chorionic pad is chemically made of hyaluronic acid, a hygroscopic compound, responsible to protect them from desiccation over time. Two commercial products with hygroscopic properties, hydrolyzed collagen, and Hyalurosmooth®, both were tested to assess their ability to prolong egg life storage for A. aegypti and A. albopictus. Results showed that 85–95% of Ae. aegypti eggs were able to hatch up to week 8 after being treated with both hydrophilic compounds, compared with the control 66.3%. These two substances showed promising effects for keeping Ae. aegypti eggs viable during prolonged storage in mass rearing insect production focused on vector control SIT programs.
Integrated Management of Malaria Vectors in Africa
19971R. Mbabazi, K. Maredia, B. B. El-Sayed, A. K. Babumba, M. Savadogo and O. Akinbo, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 11:36:56.
Malaria disease is a major public health burden in Africa. The control of malaria vectors is a critical component for prevention, management, and eradication of malaria disease. This chapter presents information on the current status of malaria vector control in Africa with emphasis on integrated vector management (IVM) programs. The chapter highlights innovative and emerging technologies such as sterile insect technique, gene drive, Wolbachia-based biological control, and other technologies for malaria vector control in Africa which can be integrated into IVM programs. The chapter also provides global resources on malaria vector management programs.
Advances in Aedes Mosquito Vector Control Strategies Using CRISPR/Cas9
19929P. D. S. U. Wickramasinghe, G. N. Silva, Y. I. N. Silva Gunawardene and R. S. Dassanayake, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 09:39:52.
Advancements in genetic engineering have resulted in the development of mosquitoes with impaired vector competence, thereby limiting acquisition and transmission of pathogens. The main dengue (DENV) vector, Aedes aegypti, is an invasive species that have spread unwittingly across the world as a result of human trade and travel. The Ae. aegypti mosquito species has spread across tropical and subtropical regions, with higher presence in urban regions where rapid breeding patterns have shown in artificial containers. Identification of and treating an adequate number of mosquito breeding sites as a control measure have been done for the past couple of years, and yet improvement is far from the expectations, even with well-funded and well-organized initiatives. In order to stop the pathogen transmission, genetically modified mosquitoes (GMM) needs to be created and released. Despite many Aedes-related achievements, GMM creation has been challenging. The spread of particular genetic elements that impair vector competence, trigger deleterious recessive mutations, or skew a population's sex ratio can be used to prevent the spread of vector disease, or eradicate invasive organisms in a species-specific and eco-friendly manner. In recent years, genome editing strategies have evolved to make use of a variety of nucleases, ranging from sequence-specific zinc finger nucleases to modular TALENs (transcription activator-like effector nucleases) and most recently, RNA-guided nucleases adapted from bacterial adaptive immune systems, dubbed CRISPR/Cas (clustered regularly interspaced palindromic repeats/CRISPR associated systems). By combining these methods, a new era in gene editing had emerged. Generally, both of these gene editing technologies utilize sequence-specific nucleases to generate double-stranded DNA breaks (or nicks) in the target sequence, resulting in desired DNA modifications using endogenous DNA repair mechanisms. Since cells with DNA lesions are unable to divide further, the nuclease-generated strand breaks must be rapidly repaired by the cell to maintain the viability. CRISPR/Cas has been widely accepted for use in a variety of organisms, including insect species, with only minor optimization steps needed thus far. CRISPR/Cas9 technology transformed the process of engineering nucleases capable of cleaving complex genomic sequences. A complementary guide RNA (gRNA) directs the Cas9 endonuclease's operation to the specific DNA target site, enabling the editing of virtually any DNA sequence without complex protein engineering and selection procedures. Apart from genome editing, the specificity and flexibility of the CRISPR/Cas9 method enables unprecedented rapid development of genetically modified organisms with mutation systems for disease vector insect control. The stability and expression of the gene construct generated by CRISPR/Cas9 or any other method must be addressed before GMM are released, in order to make sure that pathogen transmission and formulation are interrupted robustly and completely. Spreading foreign antipathogen genes through gene drive strategies among wild mosquito populations strengthens the case for a more streamlined approach. Major fields that must be adequately assessed include risk evaluation and management, conducting studies to ensure human and environmental protection, developing effective control strategies built on comprehensive gene-driving systems, and adequately addressing the ethical, legal, and social consequences of GMM release. Although GMM is theoretically feasible as a disease control method, field releases should be made only when strong scientific evidence of human and environmental protection and effectiveness are presented, and public acceptance is addressed appropriately. This chapter discusses the diverse technological advances in generating Ae. aegypti mosquitoes which are resistant to dengue virus (DENV) and other diseases, as well as the biosafety and risk assessment of these procedures. Additionally, the chapter outlines a convincing path forward for developing successful genetic-based DENV control strategies based on CRISPR/Cas9, which could be expanded to control other arboviruses while maintaining biosafety.
Genetic Improvements to the Sterile Insect Technique (SIT) for the Control of Mosquito Population
19927P. V. D. Dilani, Y. I. N. S. Gunawardene and R. S. Dassanayake, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 09:33:58.
Mosquito-borne diseases are becoming a major health problem worldwide. At present, the principal method of controlling these diseases entirely depends on the mosquito vector control strategies. However, traditional control methods which are focussed on reducing mosquito populations through environmental management and the application of insecticides are largely ineffective. Hence, various control methods, including the release of sterile insect technique (SIT), have been proposed for the reduction of the mosquito population. As a species-specific control strategy, SIT offers considerable environmental benefits and a chemical-free option for insect control. However, the application of the SIT to mosquito control consistently suffered from lack of efficient sexing system, high fitness cost and operational difficulty in ionizing radiation, density-dependent nature of the target mosquito population and various other technical issues. The intervention of genetic engineering has led to several improvements in the operation or security of SIT programmes. The advent of mosquito transgenesis has paved the way for novel approaches in mosquito control. One possibility is a release of insects carrying dominant lethal (RIDL) strategy by engineering self-limiting gene, which offers solutions for many drawbacks of traditional SIT by providing genetic sterilization, genetic sexing, genetic containment and provision of genetic markers while maintaining its environmentally benign and species-specific utility. The success of this strategy often depends on how genetic modification affects the fitness of the mosquitoes. With several improvements and modifications allowing minimum fitness load, RIDL is now available for a wide range of mosquitoes such as Aedes aegypti, Aedes albopictus and Anopheles stephensi with field-testing possibilities. However, with solid epidemiological evidence and community support, widespread implementation of these strategies might reverse the current alarming global mosquito vector-borne diseases.
Field Trials of Gene Drive Mosquitoes: Lessons from Releases of Genetically Sterile Males and Wolbachia-infected Mosquitoes
19925J. M. Marshall and V. N. Vásquez, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 09:27:08.
The discovery of CRISPR-based gene editing and its application to homing-based gene drive has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. At the same time, CRISPR-based gene editing has enabled a range of self-limiting gene drive systems to be engineered with much greater ease, including (1) threshold-dependent systems, which tend to spread only when introduced above a certain threshold population frequency, and (2) temporally self-limiting systems, which display transient drive activity before being eliminated by virtue of a fitness cost. As these CRISPR-based gene drive systems are yet to be field-tested, plenty of open questions remain to be addressed, and insights can be gained from precedents set by field trials of other novel genetics-based and biological control systems, such as trials of Wolbachia-transfected mosquitoes, intended for either population replacement or suppression, and trials of genetically sterile male mosquitoes, either using the RIDL system (release of insects carrying a dominant lethal gene) or irradiation. We discuss lessons learned from these field trials and implications for a phased exploration of gene drive technology, including homing-based gene drive, chromosomal translocations, and split gene drive as a system potentially suitable for an intermediate release.
Arthropods of Medical Importance: Need for Genetic and Other Innovative Vector Control Technologies, with Emphasis on Eco-biosocial and Environmental Considerations.
19923B. K. Tyagi, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 09:22:08.
Among the world’s known vector groups, viz. arthropods, snails and rodents, the most important vectors originate from arthropods, the jointed legs. Arthropods are doubtlessly regarded as the most dominant creatures on the Earth due largely to their remarkable structural and behavioural diversity, besides humongous species preponderance. Of course, some of these arthropods are serious pests and/or vectors of human and animal diseases—deadly, debilitating and economy destructing. According to an estimate, arthropod species make approximately 80% of the global biological diversity. Born some 350–400 million years ago, they have of course achieved, to the utter envy of all other animal forms, a formidable genetic diversity and robustness so much so that they have virtually captivated pivotal human attention for centuries. They serve as a spectacular model of bioprospecting or laboratory experiments mostly because they are found in abundance, breed prodigiously and are exceptionally easier to culture or cultivate. For the aforesaid reasons, arthropods are also the easy target for genetic manipulations such as the transgenesis (using the release of insect carrying dominant lethal (RIDL) gene system or gene drive-based genome editing, e.g. CRISPR/Cas9, to suppress or replace the vector population) or paratransgenesis (e.g. deploying endosymbiont Wolbachia-induced cytoplasmic incompatibility for replacing natural vector population). In particular, the advent of CRISPR technology has excited the potential to engineer new game-changing technologies and innovative systems that can be used to control wild populations of mosquitoes. Two developments of particular interest are a self-limiting system termed precision-guided sterile insect technique (pgSIT) and a homing-based gene drive (HGD). The unique features of these systems can make them valuable tools to control vector mosquitoes in the future. All these biotechnological advancements in vector control are designed to fit well in the multi-methodical integrated vector management (IVM) strategy.
Genetically Modified and other Innovative Vector Control Technologies
19912B. K. Tyagi, SpringerLink, 2021-12-21 08:48:19.
This book comprehensively covers the latest development in developing and deploying the genetically modified vectors, particularly Anopheles and Aedes mosquitoes responsible for transmitting malaria parasites and dengue viruses, the most deadly and/or debilitating among all the vector-borne diseases. It is considered timely and commensurate to bring about a book dealing with the various ecological, biological and social as well as regulatory aspects for the deployment of genetically modified vectors in special context with the biosafety of humans, his associates, and the environment. Written by an array of specialists and experts in various subjects of genetically modified organisms, this book centrally addresses the (i) basic principles of the genetic manipulation of vectors and they are potential impact on human and the environment, (ii) ecological, biological, ethical, legal and social implications of the use of genetically modified vectors, (iii) identification of potential hazards; assessment and management of risks for human and environment; risk/benefit analysis, (iv) principles and practices for the assessment and management of biosecurity and biosafety in laboratories (and in the field), (v) guiding principles for creation and management of institutional or national biosafety review boards and ethics review committees, and (vi) development and application of a biosafety regulatory framework and its related legal principles at national levels for securing the development and use of vector control methods based on genetic modification strategies.
How Israelis help the world fight mosquito-borne diseases
19690A. K. Leichman, ISRAEL21c, 2021-12-14 18:22:37.
Israeli scientists and entrepreneurs understand the problems and risks and have been developing a series of ingenious remedies to this growing problem. Prof. Philippos Aris Papathanos, head of Hebrew University’s Insect Genetics Lab, was awarded a Bill & Melinda Gates Foundation grant to develop new genetic approaches for controlling malaria mosquito populations. “We’re building a modern variant of an old idea that has been around since the 1950s: to control mosquitoes by modifying and manipulating their genetics,” Papathanos tells ISRAEL21c. He explains that sterilizing and releasing individual male mosquitoes theoretically leads to the collapse of the population. But this tactic has proven difficult to upscale to the necessary level of a whole city, country or continent. Instead of sterilization, Papathanos’ lab is using cutting-edge CRISPR technology to modify male malaria mosquitoes’ Y chromosome so that they produce only male babies, and those sons inherit the altered chromosome. Over time, there will be no more females and hence no more disease-transmitting bites.“This method can suppress the population in a stronger way because the genes are designed to spread through the population. We don’t need to upscale if we make the system more efficient with the least number of insects released,” says Papathanos.
Towards Integrated Management of Dengue in Mumbai
19735P. N. Paradkar, P. R. Sahasrabudhe, M. Ghag Sawant, S. Mukherjee and K. R. Blasdell, Viruses, 13. 2021-12-04 13:10:23.
With increasing urbanisation, the dengue disease burden is on the rise in India, especially in large cities such as Mumbai. Current dengue surveillance in Mumbai includes municipal corporation carrying out specific activities to reduce mosquito breeding sites and the use of insecticides to suppress the adult mosquito populations. Clinical cases remain either underreported or misreported due to the restriction to government clinics, missing the large private health care sector. There is a need for an integrated approach to manage dengue outbreaks in Mumbai. There are various novel strategies available for use that can be utilised to improve disease detection, mosquito surveillance, and control of mosquito-borne diseases. These novel technologies are discussed in this manuscript. Given the complex ecosystem of mosquito-borne diseases in Mumbai, integrating data obtained from these technologies would support the ongoing mosquito control measures in Mumbai.
Wolbachia cifB induces cytoplasmic incompatibility in the malaria mosquito vector
19439K. L. Adams, D. G. Abernathy, B. C. Willett, E. K. Selland, M. A. Itoe and F. Catteruccia, Nature Microbiology, 6:1575-1582. 2021-11-26 20:50:59.
Wolbachia, a maternally inherited intracellular bacterial species, can manipulate host insect reproduction by cytoplasmic incompatibility (CI), which results in embryo lethality in crosses between infected males and uninfected females. CI is encoded by two prophage genes, cifA and cifB. Wolbachia, coupled with the sterile insect technique, has been used in field trials to control populations of the dengue vector Aedes albopictus, but CI-inducing strains are not known to infect the malaria vector Anopheles gambiae. Here we show that cifA and cifB can induce conditional sterility in the malaria vector An. gambiae. We used transgenic expression of these Wolbachia-derived genes in the An. gambiae germline to show that cifB is sufficient to cause embryonic lethality and that cifB-induced sterility is rescued by cifA expression in females. When we co-expressed cifA and cifB in male mosquitoes, the CI phenotype was attenuated. In female mosquitoes, cifB impaired fertility, which was overcome by co-expression of cifA. Our findings pave the way towards using CI to control malaria mosquito vectors.
High Temperature Cycles Result in Maternal Transmission and Dengue Infection Differences Between Wolbachia Strains in Aedes aegypti
19221M. V. Mancini, T. H. Ant, C. S. Herd, J. Martinez, S. M. Murdochy, D. D. Gingell, E. Mararo, P. C. D. Johnson and S. P. Sinkins, mBio, e0025021. 2021-11-10 21:39:39.
Environmental factors play a crucial role in the population dynamics of arthropod endosymbionts, and therefore in the deployment of Wolbachia symbionts for the control of dengue arboviruses. The potential of Wolbachia to invade, persist, and block virus transmission depends in part on its intracellular density. Several recent studies have highlighted the importance of larval rearing temperature in modulating Wolbachia densities in adults, suggesting that elevated temperatures can severely impact some strains, while having little effect on others. The effect of a replicated tropical heat cycle on Wolbachia density and levels of virus blocking was assessed using Aedes aegypti lines carrying strains wMel and wAlbB, two Wolbachia strains currently used for dengue control. Impacts on intracellular density, maternal transmission fidelity, and dengue inhibition capacity were observed for wMel. In contrast, wAlbB-carrying Ae. aegypti maintained a relatively constant intracellular density at high temperatures and conserved its capacity to inhibit dengue. Following larval heat treatment, wMel showed a degree of density recovery in aging adults, although this was compromised by elevated air temperatures. IMPORTANCE In the past decades, dengue incidence has dramatically increased all over the world. An emerging dengue control strategy utilizes Aedes aegypti mosquitoes artificially transinfected with the bacterial symbiont Wolbachia, with the ultimate aim of replacing wild mosquito populations. However, the rearing temperature of mosquito larvae is known to impact on some Wolbachia strains. In this study, we compared the effects of a temperature cycle mimicking natural breeding sites in tropical climates on two Wolbachia strains, currently used for open field trials. When choosing the Wolbachia strain to be used in a dengue control program it is important to consider the effects of environmental temperatures on invasiveness and virus inhibition. These results underline the significance of understanding the impact of environmental factors on released mosquitoes, in order to ensure the most efficient strategy for dengue control.
Will freeing ourselves (forever) from mosquitoes soon be a realizable “dream”? Pros and cons of an epochal turning point – breaking latest news
19160Annonymous, Breaking Latest News, 2021-11-05 14:34:10.
Also true for a dangerous insect like the mosquito: due to the pathologies of which vector, such as the malaria, the dengue o la yellow fever, every year in the world about 800 thousand people die. There are therefore quite a few reasons to want to get rid of it, not just the itchy summer bites, and thanks to the technique developed by Professor Crisanti it would seem possible, in a not too distant future. It starts from a premise: Not that we want to get rid of all mosquitoes. There are around 3,500 species of mosquitoes and fortunately only a few transmit parasitic diseases such as malaria or others that cause diseases such as zika and dengue. So if I want to get rid of malaria I have to attack malaria. Traditionally this has been done with insecticides which have shown all their limits and dangers. These measures, which are apparently simple, require sustainability over time, require resources and political continuity. All this is missing today. Hence biotechnology, the idea of making mosquitoes themselves do this job. If we manage to modify the genetic characteristics of mosquitoes, we can theoretically create mosquitoes that do not reproduce or that do not transmit the infection.
Containment Practices for Arthropods Modified with Engineered Transgenes Capable of Gene Drive Addendum 1 to the Arthropod Containment Guidelines, Version 3.2
19069American Committee of Medical Entomology, Vector-Borne and Zoonotic Diseases, 2021-10-28 20:19:33.
Responsible conduct of research is a cornerstone of rigorous scientific discovery. Institutional committees, independent advisory panels, and expert steering groups are among the frameworks in academia meant to provide guidance and assurances that research activities do not result in harm to the environment, research staff, or public safety. For research involving arthropods of public health importance, several documents currently exist to guide investigators in methodologies to consider for reducing risks from arthropod escape. However, to date, there has been no standardized set of recommendations on containment practices for arthropods modified with engineered transgenes capable of gene drive. This document is meant to serve as a practical reference to fill that gap. Recommendations outlined here address containment considerations when a risk assessment indicates a possibility of establishment of a new arthropod vector species or genetically modified arthropods in the local environment.
Gene drive revolution: How genetically tweaked mosquitoes could tip the balance in the battle to contain malaria
18903F. Okumu, Genetic Literacy Project, 2021-10-06 14:24:37.
In 2016, a World Health Organisation (WHO) panel concluded that even with the best use of current approaches, there would still be 11 million malaria cases in 2050. What’s needed are longer-term integrated strategies to complement current methods. These may include large-scale environmental management to reduce Anopheles breeding, mosquito-proof homes, stronger health systems and public education focusing on disease prevention. Fortunately, new technologies are also being developed which could complement these strategies at lower cost and less effort. One particularly exciting example is the release of genetically programmed mosquitoes, which we call “protector mosquitoes”. Upon mating with wild mosquitoes they produce offspring that are either incapable of any further reproduction or unable to transmit malaria parasites.
Symbiotic Interactions Between Mosquitoes and Mosquito Viruses
18715M. Altinli, E. Schnettler and M. Sicard, Front Cell Infect Microbiol, 11:694020. 2021-09-17 14:06:45.
Mosquitoes not only transmit human and veterinary pathogens called arboviruses (arthropod-borne viruses) but also harbor mosquito-associated insect-specific viruses (mosquito viruses) that cannot infect vertebrates. In the past, studies investigating mosquito viruses mainly focused on highly pathogenic interactions that were easier to detect than those without visible symptoms. However, the recent advances in viral metagenomics have highlighted the abundance and diversity of viruses which do not generate mass mortality in host populations. Over the last decade, this has facilitated the rapid growth of virus discovery in mosquitoes. The circumstances around the discovery of mosquito viruses greatly affected how they have been studied so far. While earlier research mainly focused on the pathogenesis caused by DNA and some double-stranded RNA viruses during larval stages, more recently discovered single-stranded RNA mosquito viruses were heavily studied for their putative interference with arboviruses in female adults. Thus, many aspects of mosquito virus interactions with their hosts and host-microbiota are still unknown. In this context, considering mosquito viruses as endosymbionts can help to identify novel research areas, in particular in relation to their long-term interactions with their hosts (e.g. relationships during all life stages, the stability of the associations at evolutionary scales, transmission routes and virulence evolution) and the possible context-dependent range of interactions (i.e. beneficial to antagonistic). Here, we review the symbiotic interactions of mosquito viruses considering different aspects of their ecology, such as transmission, host specificity, host immune system and interactions with other symbionts within the host cellular arena. Finally, we highlight related research gaps in mosquito virus research.
Predicting the spread and persistence of genetically modified dominant sterile male mosquitoes
18680A. Ickowicz, S. D. Foster, G. R. Hosack and K. R. Hayes, Parasites and Vectors, 14:480. 2021-09-16 13:03:47.
Reproductive containment provides an opportunity to implement a staged-release strategy for genetic control of malaria vectors, in particular allowing predictions about the spread and persistence of (self-limiting) sterile and male-biased strains to be compared to outcomes before moving to (self-sustaining) gene-drive strains. In this study, we: (i) describe a diffusion–advection–reaction model of the spread and persistence of a single cohort of male mosquitoes; (ii) elicit informative prior distributions for model parameters, for wild-type (WT) and genetically modified dominant sterile strains (DSM); (iii) estimate posterior distributions for WT strains using data from published mark-recapture-release (MRR) experiments, with inference performed through the Delayed-Rejection Adaptive Metropolis algorithm; and (iv) weight prior distributions, in order to make predictions about genetically modified strains using Bayes factors calculated for the WT strains. If a single cohort of 5000 genetically modified dominant sterile male mosquitoes are released at the same location as previous MRR experiments with their WT counterparts, there is a 90% probability that the expected number of released mosquitoes will fall to < 1 in 10 days, and that by 12 days there will be a 99% probability that no mosquitoes will be found more than 150 m from the release location. Spread and persistence models should form a key component of risk assessments of novel genetic control strategies for malaria vectors. Our predictions, used in an independent risk assessment, suggest that genetically modified sterile male mosquitoes will remain within the locality of the release site, and that they will persist for a very limited amount of time. Data gathered following the release of these mosquitoes will enable us to test the accuracy of these predictions and also provide a means to update parameter distributions for genetic strains in a coherent (Bayesian) framework. We anticipate this will provide additional insights about how to conduct probabilistic risk assessments of stage-released genetically modified mosquitoes.
Africa must not rest until Malaria rests: What is the role of emerging technologies?
18165R. Oronje, AFIDEP, 2021-08-20 14:42:16.
As we mark the World Mosquito Day today, it is a sad reminder that Malaria still kills hundreds of thousands of people every year, majority of these people in Africa. According to the World Health Organisation (WHO), Malaria killed 409,000 people in 2019, and 94% of these deaths were in Africa. For those who survive the disease, they have many horrifying tales to tell because many get Malaria every so often, especially for those living in Malaria endemic regions. I have many horrifying tales of my experience with Malaria because I grew up in the Malaria-endemic region of Western Kenya. One of these tales is when I passed out in school when I was in Primary-4 because I had refused to take the very bitter Quinine tablets. My Mum was called to take me to hospital and by the time she arrived, I was in “hallucination mode” because all I remember is seeing two Mums lifting me up; and the next time I woke up, I was in a nearby health facility. My parents still live in this region, which means I visit them often and so every time I visit Western Kenya without taking prophylaxis, I can be sure I will come back with Malaria. But this blog is not about my horrifying Malaria tales, so I will not delve much more into that. Although many people in sub-Saharan Africa have suffered from Malaria, many are not aware of ongoing efforts to develop and test new tools with potential to eliminate Malaria. In a recent study by the African Institute for Development Policy (AFIDEP) on the “Landscape and Political Economy Analysis of Emerging Health Technologies in Sub-Saharan Africa”, we found that apart from the researchers developing these new tools and their funding agencies, other stakeholders including journalists, civil society actors, and policymakers know little, if anything, about the ongoing research on emerging health technologies, including those technologies being developed with potential to eliminate Malaria.
The Complex Lives of Mosquitoes: The Key for Malaria Control
18216F. Okumu, ISGlobal, 2021-08-19 15:19:27.
Mosquitoes spread diseases to millions of people around the world, yet they remain poorly understood by most. Studying their biology and behaviours can help us combat, and eventually eliminate, dangerous diseases such as malaria and dengue fever.There are nearly 3,500 species of mosquitoes. About 400 belong to a family called Anopheles, and of these, only about 50-70 can actually transmit malaria to humans. In Africa, where the malaria burden is highest, the most important are Anopheles gambiae, Anopheles funestus, Anopheles arabiensis and Anopheles colluzzi. Often, only one or two of these dominate malaria transmission in any country. Effective malaria control can therefore be achieved by simply identifying, understanding and then targeting just the one or two dominant Anopheles species instead of trying to kill all mosquitoes.A female Anopheles lays about 500 eggs in her lifetime, usually in standing fresh waters, although some breed along rivers or in brackish waters. The eggs weigh just 4 micrograms each and float like little pontoons on the water surfaces
New mosquito control tools are critical
18148L. Braack, Open Access Government, 2021-08-17 17:38:18.
Globally, we are making slow headway in the fight against malaria, but there has been progress, nonetheless. Since 2000, 39 countries and territories have managed to rid themselves of malaria; the most recent is China. Existing tools can achieve local elimination, but the battle is becoming harder and mosquitoes and parasites are able to change their defences, which is why we too have to constantly adapt and respond with better tools and strategies. We should also be on high alert; malaria has been distracting our attention from what will be our next global public health threat: mosquito-borne arboviruses such as Dengue, Chikungunya, Zika, Yellow Fever, West Nile Virus, Usutu, and a host of others few people have heard of. These arboviruses are spreading across the globe, each year more abundant. The mosquitoes that transmit them pose a different set of challenges, as most of them bite by day, with very different breeding habits. We must increase public awareness of the rising threat and invest much greater research effort to find ways to combat these viruses and mosquitoes.
Genetically Modified Mosquitoes
18286E. P. Caragata, Y. Lee and E. A. Buckner, UF IFAS Extension Service, 2021-08-17 14:49:18.
Genetically modified (GM) mosquitoes are controversial, partly because of misinformation. This publication provides science-based information about GM mosquitoes to the public and anyone involved in mosquito control. It explains what GM mosquitoes are and why they are being investigated as a tool for mosquito control. Describes a GM mosquito pilot project in Florida, and includes FAQs and answers explaining how GM mosquitoes are created and their potential impacts on people and the environment.
Breakthrough in non-GMO malaria control
17914C. Robinson and J. Matthews, GM Watch, 2021-07-29 15:27:47.
A just-published study carried out in a high-security lab claims to show that a CRISPR gene drive (a way of forcing a heritable genetic modification through a whole species or population) can crash populations of malaria-spreading mosquitoes. But why crash mosquito populations with a risky experimental technology if you can completely stop them spreading malaria naturally? A naturally occurring biocontrol agent – a microbe – that inhibits the development of the malaria parasite in the mosquito Anopheles arabiensis, which spreads malaria in Sub-Saharan Africa, has recently been reported in the journal Nature Communications. Among the notable features of this approach are: • The microbe doesn’t seem to harm the mosquitoes in any way • Because it doesn’t kill the mosquitoes or cut their numbers, it should not have an impact on ecosystems dependent on them for food • The microbe seems to give the mosquitoes lifelong protection from malaria infection. The researchers are based at the International Centre of Insect Physiology and Ecology (ICIPE), Kenya, and in the UK. The microbe featured in their recent publication is a microsporidian. Microsporidia are unicellular spore-forming parasites that are now recognised as fungi, or as being related to fungi. All major animal groups harbour them, particularly insects. They spread horizontally, via spores that are ingested by a new host, but many also undergo vertical transmission to the next generation, via infected eggs (known as transovarial transmission).
Transgenic expression of Nix converts genetic females into males and allows automated sex sorting in Aedes albopictus
17888C. Lutrat, R. P. Olmo, T. Baldet, J. Bouyer and E. Marois, bioRxiv, 2021.07.28.454191. 2021-07-29 12:43:42.
Aedes albopictus is a major vector of arboviruses. Better understanding of its sex determination is crucial for developing mosquito control tools, especially genetic sexing strains. In Aedes aegypti, Nix is the primary gene responsible for masculinization and Nix-expressing genetic females develop into fertile, albeit flightless, males. In Ae. albopictus, Nix has also been implicated in masculinization but its role remains to be further characterized. In this work, we established Ae. albopictus transgenic lines ectopically expressing Nix. Several were composed exclusively of genetic females, with transgenic individuals being phenotypic and functional males due to the expression of the Nix transgene. Their reproductive fitness was marginally impaired, while their flight performance was similar to controls. Overall, our results show that Nix is sufficient for full masculinization in Ae. albopictus. Moreover, the transgene construct contains a fluorescence marker allowing efficient automated sex sorting. Consequently, such strains constitute valuable sexing strains for genetic control.Competing Interest StatementThe authors have declared no competing interest.
Sex separation of Aedes spp. mosquitoes for sterile insect technique application: a review
17905B. M. Moran-Aceves, C. F. Marina, A. Dor, P. Liedo and J. Toledo, Entomologia Experimentalis Et Applicata, 10. 2021-07-24 15:04:30.
Separation of the sexes is necessary for the application of the sterile insect technique (SIT) in mosquitoes due to the hematophagous habits and disease vector activity of the females. In this review we analyze the history, current status, and future perspectives for the development of genetic sexing strains (GSS) of Aedes mosquitoes (Diptera: Culicidae). Various genetic control methods for mosquitoes are reviewed, as are their need for sex-separation methods. We focus on areas of opportunity where GSS developed with classical genetic methods can be used. Regulatory restrictions and social acceptance of various control methods are analyzed. We conclude that the development of GSS by classical methods represents the most viable option for separation of the sexes and the application of large-scale SIT programs within an area-wide integrated vector management (AW-IVM) approach.
Wolbachia as translational science: controlling mosquito-borne pathogens
17799E. P. Caragata, H. L. C. Dutra, P. H. F. Sucupira, A. G. A. Ferreira and L. A. Moreira, Trends in Parasitology, 2021-07-22 20:54:55.
In this review we examine how exploiting the Wolbachia?mosquito relationship has become an increasingly popular strategy for controlling arbovirus transmission. Field deployments of Wolbachia-infected mosquitoes have led to significant decreases in dengue virus incidence via high levels of mosquito population suppression and replacement, emphasizing the success of Wolbachia approaches. Here, we examine how improved knowledge of Wolbachia?host interactions has provided key insight into the mechanisms of the essential phenotypes of pathogen blocking and cytoplasmic incompatibility. And we discuss recent studies demonstrating that extrinsic factors, such as ambient temperature, can modulate Wolbachia density and maternal transmission. Finally, we assess the prospects of using Wolbachia to control other vectors and agricultural pest species.
Yes, genetically modified mosquitoes do exist, but they don’t bite and aren’t harmful to humans
17815E. Jones and M. Chamberlin, WKYC Studios, 2021-07-19 14:35:11.
In 2021, Oxitec, a biotechnology company that develops genetically modified insects that safely and sustainably control pests that spread disease, damage crops and harm livestock across the globe, partnered with the Florida Keys Mosquito Control District (FKMCD) to evaluate the effectiveness of Oxitec mosquitoes to control the invasive, disease-spreading Aedes aegypti mosquito in the Florida Keys. Aedes aegypti mosquitoes typically live in tropical and subtropical climates, according to the CDC. The agency says Aedes aegypti mosquitoes are more likely to spread Zika, dengue, chikungunya and other viruses than other types of mosquitoes because they live near and prefer to feed on people. “One of the things that sort of works against the Aedes aegypti is that they are anthropophilic,” said Dr. Floyd Shockley, the collections manager in the Department of Entomology at the Smithsonian National Museum of Natural History. “Most of the mosquitoes that feed on humans tend to fly at night, but Aedes aegypti flies during the day. It's actually the mosquito that you usually run into when you're out hiking.” Dr. Nathan Rose, the head of Regulatory Affairs at Oxitec, tells VERIFY the company produces genetically modified male mosquitoes to target the wild Aedes aegypti female mosquitoes because they are the main vector for viral diseases.
Combating mosquito-borne diseases using genetic control technologies
17735G.-H. Wang, S. Gamez, R. R. Raban, J. M. Marshall, L. Alphey, M. Li, J. L. Rasgon and O. S. Akbari, Nature Communications, 12:4388. 2021-07-19 13:06:45.
Mosquito-borne diseases, such as dengue and malaria, pose significant global health burdens. Unfortunately, current control methods based on insecticides and environmental maintenance have fallen short of eliminating the disease burden. Scalable, deployable, genetic-based solutions are sought to reduce the transmission risk of these diseases. Pathogen-blocking Wolbachia bacteria, or genome engineering-based mosquito control strategies including gene drives have been developed to address these problems, both requiring the release of modified mosquitoes into the environment. Here, we review the latest developments, notable similarities, and critical distinctions between these promising technologies and discuss their future applications for mosquito-borne disease control.
Gene Drives – Engineering the Wild
17825L. Sharratt, Sentinel, 2021-07-13 14:52:05.
So far, genetically engineered organisms have been mostly limited to agricultural use, with partial success. Around the world, a few major crops (mostly corn, soy, and cotton) are genetically engineered, predominantly for herbicide tolerance and insect resistance. However, the newer techniques of genome editing (also called gene editing) mean that a much wider variety of organisms can now be genetically engineered, including for many purposes outside of food and farming. This increased power is most dramatically illustrated in the development of gene drive technology. Unlike genetically engineered plants and animals intended for confined use in agricultural production, gene drive organisms are expressly designed for intentional, long-lived release into the wild. Gene drives are a technology through which a few individual genetically engineered organisms would be deployed to intentionally push new genes through an entire population of a species in the wild or in a farm ecosystem. Through the gene drive mechanism, new genes would be inherited by all offspring in subsequent generations, not just the expected half in normal inheritance. When gene drive organisms reproduce, specific traits as well as the gene drive mechanism itself would be passed on. Making such spreading genetic changes to an organism, or eliminating it in the wild, could disrupt whole ecosystems in ways that are difficult or impossible to predict or reverse.
Scientists develop new technology that gives greater control for managing malaria mosquitoes
17650Keele University, Phy Org, 2021-07-06 19:19:27.
Researchers including a Keele University scientist have engineered an innovative approach to disable highly powerful genetic devices that control harmful insect populations. Dr. Roberto Galizi from Keele's School of Life Sciences was part of a research team that previously developed gene drive technologies that proved highly effective in eliminating populations of mosquitoes in the laboratory, offering a powerful new strategy to prevent deadly vector-borne disease such as malaria. Gene drive elements inserted in the mosquito genome can rapidly spread genetic modifications, such as impairment of fertility, throughout the entire population target by biasing their genetic inheritance after mating with wild insects. The gene drive technologies show great potential for suppressing the mosquito species that transmit malaria with increased power compared to other methods, thanks to their capacity to self-spread through the population. However, this also makes it difficult to retain control of this technology once released. So to combat this, the researchers have now developed an innovative and highly effective technology that allows them to control and even reverse the effects of gene drives.
The (Losing) Battle Against Mosquitoes In Texas
17599J. Clayton, Texas Public Radio, 2021-06-26 14:13:20.
Jerry Clayton: Mosquitoes are a fact of life in Texas, and the battle against the pesky biting insects is never ending. But there are some new weapons on the horizon. Zach Adleman is an associate professor of entomology at Texas A&M University. He joins us today. Thanks for being here, Zach.
A genetically encoded anti-CRISPR protein constrains gene drive spread and prevents population suppression
17565C. Taxiarchi, A. Beaghton, N. I. Don, K. Kyrou, M. Gribble, D. Shittu, S. P. Collins, C. L. Beisel, R. Galizi and A. Crisanti, Nature Communications, 12:3977. 2021-06-25 15:00:05.
CRISPR-based gene drives offer promising means to reduce the burden of pests and vector-borne diseases. These techniques consist of releasing genetically modified organisms carrying CRISPR-Cas nucleases designed to bias their inheritance and rapidly propagate desired modifications. Gene drives can be intended to reduce reproductive capacity of harmful insects or spread anti-pathogen effectors through wild populations, even when these confer fitness disadvantages. Technologies capable of halting the spread of gene drives may prove highly valuable in controlling, counteracting, and even reverting their effect on individual organisms as well as entire populations. Here we show engineering and testing of a genetic approach, based on the germline expression of a phage-derived anti-CRISPR protein (AcrIIA4), able to inactivate CRISPR-based gene drives and restore their inheritance to Mendelian rates in the malaria vector Anopheles gambiae. Modeling predictions and cage testing show that a single release of male mosquitoes carrying the AcrIIA4 protein can block the spread of a highly effective suppressive gene drive preventing population collapse of caged malaria mosquitoes.
Fine-scale estimation of key life-history parameters of malaria vectors: implications for next-generation vector control technologies
17329A. L. Morris, A. Ghani and N. Ferguson, Parasites and Vectors, 14:311. 2021-06-08 14:48:41.
Mosquito control has the potential to significantly reduce malaria burden on a region, but to influence public health policy must also show cost-effectiveness. Gaps in our knowledge of mosquito population dynamics mean that mathematical modelling of vector control interventions have typically made simplifying assumptions about key aspects of mosquito ecology. Often, these assumptions can distort the predicted efficacy of vector control, particularly next-generation tools such as gene drive, which are highly sensitive to local mosquito dynamics.
What is wrong in extinguishing a species? Charting the Ethical Challenges of using Gene-Drive Technologies to eradicate A. gambiae vector populations
17161M. Annoni and T. Pievani, Biolaw Journal-Rivista Di Biodiritto, 2021-05-31 19:04:09.
This article analyses three ethical arguments against the use of gene-drive technologies to control for, and possibly extinguish, a particular species of vector mosquitoes (Anopheles gambiae) causing the malaria infection. We conclude that none of these arguments is truly persuasive in the specific case and, therefore, that using gene-drive technologies to suppress or eradicate the population of Anopheles gambiae could be ethically justifiable provided certain cautions referring to ecological consequences, evolutionary effects and social engagement of local communities.
Sterilizing skeeters using CRISPR/Cas9
17117H. Tasoff, Phy Org, 2021-05-24 18:45:33.
Mosquitoes are one of humanity's greatest nemeses, estimated to spread infections to nearly 700 million people per year and cause more than one million deaths. UC Santa Barbara Distinguished Professor Craig Montell has made a breakthrough in one technique for controlling populations of Aedes aegypti, a mosquito that transmits dengue, yellow fever, Zika and other viruses. The study, published in the Proceedings of the National Academy of Sciences, documents the first use of CRISPR/Cas9 gene editing to target a specific gene tied to fertility in male mosquitoes. The researchers were then able to discern how this mutation can suppress the fertility of female mosquitoes. Montell and his coauthors were working to improve a vector-control practice called the sterile insect technique (SIT). To manage populations, scientists raise a lot of sterile male insects. They then release these males in numbers that overwhelm their wild counterparts. The idea is that females that mate with sterile males before finding a fertile one are themselves rendered infertile, thereby decreasing the size of the next generation. Repeating this technique several times has the potential to crash the population. What's more, because each generation is smaller than the last, releasing a similar number of sterile males has a stronger effect over time.
Why the EU should back research into gene drive – even if Europe never uses it
17132R. Müller, The Brussels Times, 2021-05-23 12:00:13.
As the EU’s Biodiversity Strategy reaches the European Parliament, it has reopened a worrying debate about research into gene drive technology, a tool which could pave the way for biasing the inheritance of desired genetic traits through targeted species. Advances in this kind of genetic technology could allow scientists to create a blueprint for stopping diseases spread by mosquitoes and protecting endangered species, both significant reasons for supporting this emerging field. Yet even if EU decision makers see no need for gene drive technology in Europe at present, there are compelling reasons for supporting ongoing research, and rejecting irresponsible and short-sighted calls for a moratorium. Firstly, the threat of malaria and other mosquito-borne diseases may be minimal today but it existed on the continent within living memory, with Europe first becoming malaria-free in 1975, and then again only as recently as 2015.
Malaria-Resistant Mosquitoes (Diptera: Culicidae); The Principle is Proven, But Will the Effectors Be Effective?
18710Z. N. Adelman and B. B. Kojin, Journal of Medical Entomology, 58:1997-2005. 2021-05-21 13:50:24.
Over the last few decades, a substantial number of anti-malarial effector genes have been evaluated for their ability to block parasite infection in the mosquito vector. While many of these approaches have yielded significant effects on either parasite intensity or prevalence of infection, just a few have been able to completely block transmission. Additionally, many approaches, while effective against the parasite, also disrupt or alter important aspects of mosquito physiology, leading to corresponding changes in lifespan, reproduction, and immunity. As the most promising approaches move towards field-based evaluation, questions of effector gene robustness and durability move to the forefront. In this forum piece, we critically evaluate past effector gene approaches with an eye towards developing a deeper pipeline to augment the current best candidates.
Small-Cage Laboratory Trials of Genetically-Engineered Anopheline Mosquitoes
17068R. Carballar-Lejarazú, T. B. Pham, V. Bottino-Rojas, A. Adolfi and A. A. James, J Vis Exp, 2021-05-18 14:30:01.
Control of mosquito-borne pathogens using genetically-modified vectors has been proposed as a promising tool to complement conventional control strategies. CRISPR-based homing gene drive systems have made transgenic technologies more accessible within the scientific community. Evaluation of transgenic mosquito performance and comparisons with wild-type counterparts in small laboratory cage trials provide valuable data for the design of subsequent field cage experiments and experimental assessments to refine the strategies for disease prevention. Here, we present three different protocols used in laboratory settings to evaluate transgene spread in anopheline mosquito vectors of malaria. These include inundative releases (no gene-drive system), and gene-drive overlapping and non-overlapping generation trials. The three trials vary in a number of parameters and can be adapted to desired experimental settings. Moreover, insectary studies in small cages are part of the progressive transition of engineered insects from the laboratory to open field releases. Therefore, the protocols described here represent invaluable tools to provide empirical values that will ultimately aid field implementation of new technologies for malaria elimination.
Next gen insect control
16960E. Unglesbee, Progressive Farmer, 2021-05-04 14:58:12.
Dubbed "self-limiting" insects by their makers, a UK-based biotechnology company called Oxitec, these insects are genetically modified (GM) with an inserted gene that permits only male offspring to survive. Once released into a pest community, the GM insects gradually lower the population, accomplishing a new type of pest control. Then, rather politely, they die off themselves. "After we stop releasing the self-limiting males, the gene declines in a population over a short period of time and within a few generations, disappears," Neil Morrison, head of agriculture programs for Oxitec, told DTN. "It's a gene that prevents survival of half its carriers -- the females -- so it's essentially programmed to decline and disappear quite rapidly." Sound too sci-fi to be real? It's actually happening right now, in the Florida Keys. After gaining EPA and state regulatory approval for the project last year, Oxitec is working with the Florida Keys Mosquito Control District to deploy the country's first largescale release of Oxitec's self-limiting Aedes aegypti mosquitoes.
Modeling and analysis of the implementation of the Wolbachia incompatible and sterile insect technique for mosquito population suppression.
17098B. Zheng, J. S. Yu and J. Li, Siam Journal on Applied Mathematics, 81:718-740. 2021-04-29 13:06:06.
Mathematical analysis may offer guidance in designing effective mass release strategies for the area-wide application of this Wolbachia incompatible and sterile insect technique in the future. The two most crucial concerns in designing release strategies are how often and in what amount should Wolbachia-infected mosquitoes be released in order to guarantee population suppression. Motivated by the experimental data from the Guangzhou mosquito factory and the release strategy implemented on two islands, we formulate and analyze a mosquito population suppression model considering the situation for the release period T less than the sexual lifespan of Wolbachia-infected males. We define release amount thresholds g(1)* and g(2)* with g(1)* < g(2)*. When the release amount c satisfies c >= g(2)*, population suppression is always achievable, as is mathematically manifested by the global asymptotic stability of the origin. However, when c is an element of (0, g(1)*], we find that suppression can be achieved only if the initial wild mosquito population is small enough. This is mathematically proved by the local asymptotic stability of the origin, together with the existence of exactly two T-periodic solutions, one of which is asymptotically stable and the other of which is unstable, with T being the waiting period between two consecutive releases. For c is an element of (g(1)*, g(2)*), we find sufficient conditions on the nonexistence of T-periodic solution, and the existence of at most two T-periodic solutions.
Transgenic mosquito resistant to multiple serotypes of the dengue virus
34972Department of Chemistry, Faculty of Science, University of Colombo in collaboration with the Molecular Medicine Unit, Faculty of Medicine, University of Kelaniya, University of Colombo, 2021-04-10 10:39:01.
The dengue virus causes epidemics in more than 100 tropical and sub-tropical countries, where over 2.5 billion people (over 40% of the world’s population) are currently at risk of dengue infections. In recent years, dengue has become the number one vector-borne disease in Sri Lanka. The worst ever dengue virus outbreaks experienced in 2009, 2010, and 2013 transformed dengue into a major health issue in Sri Lanka. There are no medicines or effective vaccines developed for dengue; therefore, mosquito vector control is the most promising option to control dengue virus transmission. The conventional vector control methods used currently have only limited success. In an attempt to find a solution to this problem, the research team lead by Professor Ranil Dassanayake, Department of Chemistry, University of Colombo in collaboration with Professor Nilmini Gunawardene, Molecular Medicine Unit, Faculty of Medicine, University of Kelaniya undertook to develop a dengue virus resistant transgenic Aedes aegypti mosquito (the primary vector of dengue virus transmission) line using an RNA interference (RNAi) based technology, as a component of the Ph.D. research project of Mr. Kalindu Ramyasoma.
Evidence for natural hybridization and novel Wolbachia strain superinfections in the Anopheles gambiae complex from Guinea
16990C. L. Jeffries, C. Cansado-Utrilla, A. H. Beavogui, C. Stica, E. K. Lama, M. Kristan, S. R. Irish and T. Walker, Royal Society Open Science, 8:18. 2021-04-07 14:55:09.
Wolbachia, a widespread bacterium which can influence mosquito-borne pathogen transmission, has recently been detected within Anopheles (An.) species that are malaria vectors in Sub-Saharan Africa. Although studies have reported Wolbachia strains in the An. gambiae complex, apparent low density and prevalence rates require confirmation. In this study, wild Anopheles mosquitoes collected from two regions of Guinea were investigated. In contrast with previous studies, RNA was extracted from adult females (n = 516) to increase the chances for the detection of actively expressed Wolbachia genes, determine Wolbachia prevalence rates and estimate relative strain densities. Molecular confirmation of mosquito species and Wolbachia multilocus sequence typing (MLST) were carried out to analyse phylogenetic relationships of mosquito hosts and newly discovered Wolbachia strains. Strains were detected in An. melas (prevalence rate of 11.6%-16/138) and hybrids between An. melas and An. gambiae sensu stricto (prevalence rate of 40.0%-6/15) from Senguelen in the Maferinyah region. Furthermore, a novel high-density strain, termed wAnsX, was found in an unclassified Anopheles species. The discovery of novel Wolbachia strains (particularly in members, and hybrids, of the An. gambiae complex) provides further candidate strains that could be used for future Wolbachia-based malaria biocontrol strategies.
CRISPR-mediated knock-in of transgenes into the malaria vector Anopheles funestus
16674C. Quinn, A. Anthousi, C. Wondji and T. Nolan, bioRxiv, 2021.03.31.437891. 2021-03-31 13:57:08.
We describe herein an optimised transformation system based on the germline delivery of CRISPR components that allows efficient cleavage of a previously validated genomic site and preferential repair of these cut sites via homology-directed repair (HDR), which allows introduction of exogenous template sequence, rather than end-joining repair. The rates of transformation achieved are sufficiently high that it should be able to introduce alleles of choice to a target locus, and recover these, without the need to include additional dominant marker genes. Moreover, the high rates of HDR observed suggest that gene drives, which employ an HDR-type mechanism to ensure their proliferation in the genome, may be well suited to work in An. funestus.Competing Interest StatementThe authors have declared no competing interest.
Current Effector and Gene-Drive Developments to Engineer Arbovirus-Resistant Aedes aegypti (Diptera: Culicidae) for a Sustainable Population Replacement Strategy in the Field
16596W. R. Reid, K. E. Olson and A. W. E. Franz, J Med Entomol, 2021-03-12 20:35:28.
Conventional mosquito control efforts based on insecticide treatments and/or the use of bednets and window curtains are currently insufficient to reduce arbovirus prevalence in affected regions. Novel, genetic strategies that are being developed involve the genetic manipulation of mosquitoes for population reduction and population replacement purposes. Population replacement aims at replacing arbovirus-susceptible wild-type mosquitoes in a target region with those that carry a laboratory-engineered antiviral effector to interrupt arboviral transmission in the field.
When More is Less: Mosquito Population Suppression Using Sterile, Incompatible and Genetically Modified Male Mosquitoes
18708S. L. Dobson, Journal of Medical Entomology, 58:1980-1986. 2021-03-11 13:50:08.
The current review of the Sterile Insect Technique (SIT) is motivated by new technologies and the recent renaissance of male release field trials, which is driving an evolution in mosquito control and regulation. Practitioners that are releasing male mosquitoes would do well to learn from past successes and failures, including political and public engagement complications. With examples that include nuanced integrations of the different technologies, e.g., combinations of Wolbachia and irradiation, it is critical that scientists understand and communicate accurately about the technologies, including their evolving management by different regulatory agencies in the USA. Some male release approaches are considered ‘pesticides’ and regulated by federal and state agencies, while other male release approaches are unregulated. It is important to consider how the new technologies fit with the more ‘traditional’ chemical applications of adulticides and larvicides. The economics of male release programs are substantially different from traditional control costs, which can be a challenge to their adoption by abatement districts. However, there is substantial need to overcome these complications and challenges, because the problem with invasive mosquitoes grows ever worse with factors that include insecticide resistance, globalization and climate change.
femaleless Controls Sex Determination and Dosage Compensation Pathways in Females of Anopheles Mosquitoes
16910E. Krzywinska, L. Ferretti, J. Li, J.-C. Li, C.-H. Chen and J. Krzywinski, Current Biology, 31:1084-1091.e4. 2021-03-08 18:07:47.
Here we show that in the African malaria mosquito Anopheles gambiae, a gene, which likely arose in the Anopheles lineage and which we call femaleless (fle), controls sex determination in females by regulating splicing of dsx and fruitless (fru; another terminal gene within a branch of the sex determination pathway). Moreover, fle represents a novel molecular link between the sex determination and dosage compensation pathways. It is necessary to suppress activation of dosage compensation in females, as demonstrated by the significant upregulation of the female X chromosome genes and a correlated female-specific lethality, but no negative effect on males, in response to fle knockdown. This unexpected property, combined with a high level of conservation in sequence and function in anopheline mosquitoes, makes fle an excellent target for genetic control of all major vectors of human malaria.
Sex Determination and Dosage Compensation: femaleless Is the Link in Anopheles Mosquitoes
16908M. Scott, Current Biology, 31:R260-R263. 2021-03-08 18:03:44.
A new study finds that the femaleless gene is essential for sexual development and repression of X-chromosome dosage compensation in the malaria vector Anopheles gambiae. This could provide the basis for a new genetic approach to control this pest.
Eliminating Mosquitoes with Precision Guided Sterile Males
16563M. Li, T. Yang, M. Bui, S. Gamez, T. Wise, N. P. Kandul, J. Liu, L. Alcantara, H. Lee, J. R. Edula, R. Raban, Y. Zhan, Y. Wang, N. DeBeaubien, J. Chen, H. M. Sanchez C, J. B. Bennett, I. Antoshechkin, C. Montell, J. M. Marshall and O. S. Akbari, bioRxiv, 2021.03.05.434167. 2021-03-06 20:07:26.
Here we develop a molecular genetic control system termed precision guided sterile insect technique (pgSIT) in Aedes aegypti. PgSIT uses a simple CRISPR-based approach to generate sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and eliminate mosquitoes in multigenerational population cages. This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable, and reversible manner.
In Uganda, genetically modified mosquitoes bring hope and fear
16550Anonymous, africanews, 2021-03-05 19:32:29.
Scientists here are investigating whether populations of the malaria-carrying insects can be reduced by genetic modification. They're looking at the viability of releasing large numbers of genetically modified mosquitos into the wild to influence future generations. The study is being led by scientists here at the institute in Kampala with researchers from the Target Malaria group. Dr. Jonathan Kayondo is the principal investigator managing the project. He says the disease can be deadly for children, especially those under five-years-old. "The aim here is to develop a new vector control tool for the suppression of malaria transmission," says Dr. Jonathan Kayondo.
Knowledge, Attitude, and Practices Survey in Greece before the Implementation of Sterile Insect Technique against Aedes albopictus
16661A. Stefopoulou, S. L. LaDeau, N. Syrigou, G. Balatsos, V. Karras, I. Lytra, E. Boukouvala, D. P. Papachristos, P. G. Milonas, A. Kapranas, P. Vahamidis and A. Michaelakis, Insects, 12. 2021-03-02 13:52:16.
A KAP tool was used to shed light on the knowledge, practices, and attitudes of local community members in order to better prepare and motivate participation in household mosquito control and to assess current understanding of SIT. Each household also received specific information about mosquito source habitat in their own yards at the time of the initial KAP survey. These household data were complemented by standardized mosquito trapping in the municipality. Our findings indicate that citizens’ attitude toward SIT ranged from indecisive to fully supportive, while 77.5% of the respondents agreed that the SIT has many advantages over chemical control methods. Furthermore, the results demonstrate that using the door-to-door campaign as an intervention and prerelease method before SIT can suppress the initial mosquito population and potentially improve its efficacy. Lastly, we show that the presence of local municipality officials during door-to-door visits was associated with increased willingness from the residents to participate in the intervention.
Sterile Insect Technique: Lessons From the Past
18706M. Q. Benedict, Journal of Medical Entomology, 58:1974-1979. 2021-02-25 13:35:08.
When E.F. Knipling conceived of the release of sexually sterile insects to suppress wild populations, he laid down several fundamental qualities that characterized suitable target species—some of which mosquitoes generally violate—including high reproductive rates and large population numbers. Regardless of this, their global importance in public health has led numerous research teams to attempt to use the mosquito sterile insect technique against several species. Because of the degree of financial commitment required for suppression programs, most releases have consisted of preliminary investigations of male performance, population characteristics, and production methods. Those that have accomplished suppression provide important insights regarding the challenges of production, dispersal, and immigration. Insights gained from these studies remain relevant today, regardless of the genetic control technology being applied. In this article, I highlight studies that were notable for the insights that were gained, the intrinsic difficulties that mosquitoes present, and synthesize these into recommendations for successful applications of the sterile insect technique and newer technologies to mosquitoes.
Sterile Insect Technique (SIT) against Aedes Species Mosquitoes: A Roadmap and Good Practice Framework for Designing, Implementing and Evaluating Pilot Field Trials
16659C. F. Oliva, M. Q. Benedict, C. M. Collins, T. Baldet, R. Bellini, H. Bossin, J. Bouyer, V. Corbel, L. Facchinelli, F. Fouque, M. Geier, A. Michaelakis, D. Roiz, F. Simard, C. Tur and L.-C. Gouagna, Insects, 12. 2021-02-24 13:44:35.
We offer here a pragmatic and accessible ‘roadmap’ for the pre-pilot and pilot phases to guide any interested party. This will support stakeholders, non-specialist scientists, implementers, and decision-makers. Applying these concepts will ensure, given adequate resources, a sound basis for local field trialing and for developing experience with the technique in readiness for potential operational deployment. This synthesis is based on the available literature, in addition to the experience and current knowledge of the expert contributing authors in this field. We describe a typical path to successful pilot testing, with the four concurrent development streams of Laboratory, Field, Stakeholder Relations, and the Business and Compliance Case. We provide a graphic framework with criteria that must be met in order to proceed.
Mosquitoes genetically modified to be resistant to Zika
16259Staff, Lab+Life Scientist, 2021-02-02 15:55:50.
Researchers have wrestled with different strategies for controlling the spread of Zika virus, which is transmitted to humans from female mosquito bites. One approach, which has been approved by the US Environmental Protection Agency, will see more than 750 million genetically modified mosquitoes released into the Florida Keys in 2021 and 2022. These ‘suicide mosquitoes’ are genetically altered to produce offspring that die before emerging into adults and therefore cannot bite humans and spread disease.
Regulating the expression of gene drives is key to increasing their invasive potential and the mitigation of resistance
16290A. Hammond, X. Karlsson, I. Morianou, K. Kyrou, A. Beaghton, M. Gribble, N. Kranjc, R. Galizi, A. Burt, A. Crisanti and T. Nolan, PLOS Genetics, 17:e1009321. 2021-01-29 21:53:25.
Here we show that restricting the cutting activity of the gene drive to the germline tissue is crucial to maintaining its potency and we illustrate how failure to restrict this activity can lead to the generation of mutations that can make mosquitoes resistant to the gene drive.
Sexual Competitiveness and Induced Egg Sterility by Aedes aegypti and Aedes albopictus Gamma-Irradiated Males: A Laboratory and Field Study in Mexico
17760J. G. Bond, S. Aguirre-Ibáñez, A. R. Osorio, C. F. Marina, Y. Gómez-Simuta, R. Tamayo-Escobar, A. Dor, P. Liedo, D. O. Carvalho and T. Williams, Insects, 12. 2021-01-29 14:44:07.
The sterile insect technique may prove useful for the suppression of mosquito vectors of medical importance in regions where arboviruses pose a serious public health threat. In the present study, we examined the effects of sterilizing irradiation doses across different ratios of fertile:irradiated males on the mating competitiveness of Ae. aegypti and Ae. albopictus under laboratory and field-cage conditions. For both species, the percentage of females inseminated and the number of eggs laid over two gonotrophic cycles varied significantly in mating treatments involving 1:1, 1:5, and 1:10 fertile:irradiated males compared to controls of entirely fertile or entirely irradiated males but was not generally affected by the irradiation dose. Egg hatching was negatively affected in females exposed to increasing proportions of irradiated males in both laboratory and field cages. Male competitiveness (Fried’s index) values varied from 0.19 to 0.58 in the laboratory and were between 0.09 and 1.0 in field cages, depending on th species. Competitiveness values were negatively affected by th eirradiation dose in both species under field-cage conditions, whereas in the laboratory, Ae. albopictus was sensitive to the dose but Ae. aegypti was not. In general, male competitiveness was similar across all mating regimes. Most importantly, induced egg sterility was positively correlated with the proportion of irradiated males present in the mating treatments, reaching a maximum of 88% under field-cage conditions for both Ae. aegypti and Ae. albopictus males treated with 50 and 40 Gy irradiation, respectively. These results indicate that sterile males produced at our facility are suitable and competitive enough for field pilot SIT projects and provide guidance to decide the optimal sterile:fertile ratios.
Genetically-modified mosquitoes key to stopping Zika virus spread
16208University of Missouri, Medical Xpress, 2021-01-26 13:52:44.
Alexander Franz, an associate professor in the MU College of Veterinary Medicine, collaborated with researchers at Colorado State University by using CRISPR gene-editing technology to produce mosquitoes that are unable to replicate Zika virus and therefore cannot infect a human through biting. "We genetically manipulated these mosquitoes by inserting an artificial gene into their genome that triggers one of the immune pathways in the midgut to recognize and destroy the RNA genome of Zika virus," Franz said. "By developing these mosquitoes that are resistant to the virus, the disease cycle is interrupted so transmission to humans can no longer take place." Franz added that the genetic modification is inheritable, so future generations of the altered mosquitoes would be resistant to Zika virus as well.
Exploring Gene Drive Technologies in Agriculture, Biodiversity and Human Disease
15963The GBIRd Partnership and The GeneConvene Global Collaborative, Gene Drive Research Forum, 2021-01-14 21:37:12.
The GBIRd Partnership and The GeneConvene Global Collaborative recently collaborated through The Gene Drive Research Forum, to create and produce an engaging conversation between Drs. Fred Gould and Charles Godfray about gene drive technologies – the potential benefits and complicating factors for agriculture, biodiversity, and human disease.
CRISPR and the splice to survive: New gene-editing technology could be used to save species from extinction—or to eliminate them.
16011E. Kolbert, New Yorker, 2021-01-11 14:25:59.
About a year ago, not long before the pandemic began, I paid a visit to the center, which is an hour southwest of Melbourne. The draw was an experiment on a species of giant toad known familiarly as the cane toad. The toad was introduced to Australia as an agent of pest control, but it promptly got out of control itself, producing an ecological disaster. Researchers at the A.C.D.P. were hoping to put the toad back in the bottle, as it were, using crispr.
Double drives and private alleles for localised population genetic control
15945K. Willis and A. Burt, bioRxiv, 2021.01.08.425856. 2021-01-09 16:30:16.
In this paper we propose and model a series of low threshold double drive designs for population suppression, each consisting of two constructs, one imposing a reproductive load on the population and the other inserted into a differentiated locus and controlling the drive of the first. Simple deterministic, discrete-generation computer simulations are used to assess the alternative designs. We find that the simplest double drive designs are significantly more robust to pre-existing cleavage resistance at the differentiated locus than single drive designs, and that more complex designs incorporating sex ratio distortion can be more efficient still, even allowing for successful control when the differentiated locus is neutral and there is up to 50% pre-existing resistance in the target population. Similar designs can also be used for population replacement, with similar benefits. A population genomic analysis of PAM sites in island and mainland populations of the malaria mosquito Anopheles gambiae indicates that the differentiation needed for our methods to work can exist in nature. Double drives should be considered when efficient but localised population genetic control is needed and there is some genetic differentiation between target and non-target populations.
Self-Deleting Genes Project To Tackle Mosquito-Borne Diseases
15923D. Ozdemir, INTERESTING ENGINEERING, 2021-01-08 18:58:57.
Did you know that mosquitoes kill at least 725,000 persons every year? They truly are one of the world's deadliest animals which is the reason why scientists from all around are trying to find new ways of dealing with them. Controlling mosquito populations and preventing them from transmitting disease at times through genetic engineering is one way of doing that. Now, a new Texas A&M AgriLife Research project has plans of enabling "test runs" of the proposed changes in mosquitoes that are automatically deleted from their genetic code. Researchers have used genetic engineering in the past to modify mosquitoes in a way that they pass on infertility, don't grow wings, can't spread malaria, or have impaired smell. However, as New Atlas reports, this sort of modification can have harmful consequences that may be impossible to reverse when released into the wild.
Mosquito Sexual Selection and Reproductive Control Programs
15921L. J. Cator, C. A. S. Wyer and L. C. Harrington, Trends in Parasitology, 2021-01-06 18:45:40.
Recent work has generated many key insights about specific aspects of mating behavior and physiology. Here, we synthesize these findings and classify swarming mosquito systems as polygynous. Male mating success is highly variable in swarms and evidence suggests that it is likely determined by both scramble competition between males and female choice. Incorporating this new understanding will improve both implementation and long-term stability of reproductive control tools.
His Passion Was Contagious
15928D. C. McCool, Notre Dame Magazine, 2021-01-01 19:03:35.
Craig was an entomologist and vector biologist whose interest in mosquitoes and the diseases they transmit to people was as contagious as the pathogens themselves. Hesburgh could not have chosen a more driven faculty member. In his 38 years at Notre Dame, before he died in 1995 at an Entomology Society of America conference in Las Vegas, Craig cultivated a legacy in a field that was in its infancy. His personality attracted even more people dedicated to eliminating mosquito-borne diseases, and the circle widened in unexpected ways. The Chicago native directed more than 40 doctoral students and mentored 38 postdoctoral researchers. He created Notre Dame’s Vector Biology Laboratory — vectors pass diseases from one organism to another — with a focus on the Aedes genus of mosquitoes. He became Notre Dame’s first member of the prestigious National Academy of Sciences (NAS). And he developed a program that has turned out hundreds of new field biologists who have gone onto careers in academia and public health.
Self-deleting genes promise risk-free genetic engineering of mosquitoes
15852D. Quick, New Atlas, 2020-12-29 18:53:49.
A new project by Texas A&M AgriLife Research is looking to enable "test runs" of genetic changes to mosquitoes that are automatically deleted. Various angles of attack using genetic engineering to combat mosquitoes have been pursued in recent years, including modifying them so they pass on infertility, don't grow wings, can't spread malaria or have impaired smell. But making genetic modifications to an organism and then releasing them into the wild runs the risk of unintended and harmful consequences that may be difficult to reverse. That's where the new Texas A&M AgriLife Research project comes in. It is looking to enable "test runs" of genetic modifications that would then automatically be deleted from the mosquitoes' genetic code after a period of time.
Self-deleting genes to be tested as part of mosquito population control concept
15926B. Hays, UPI, 2020-12-28 18:59:14.
Scientists at Texas A&M have developed a new technique for altering the genes of mosquitoes -- the new technology will cause genetic changes to self-delete from the mosquitoes' genome. Thanks to the breakthrough, described Monday in the Philosophical Transactions of the Royal Society B, researchers can now test-run experimental gene edits without permanently altering a mosquito's genome."People are wary of transgenes spreading in the environment in an uncontrolled manner. We feel that ours is a strategy to potentially prevent that from happening," Zach Adelman, professor of entomology at the Texas A&M College of Agriculture, said in a news release. "The idea is, can we program a transgene to remove itself? Then, the gene won't persist in the environment."
$3.9M project on self-deleting genes takes aim at mosquito-borne diseases
15847O. Kuchment, AGRILIFE Today, 2020-12-28 18:52:03.
To control mosquito populations and prevent them from transmitting diseases such as malaria, many researchers are pursuing strategies in mosquito genetic engineering. A new Texas A&M AgriLife Research project aims to enable temporary “test runs” of proposed genetic changes in mosquitoes, after which the changes remove themselves from the mosquitoes’ genetic code. The project’s first results were published on Dec. 28 in Philosophical Transactions of the Royal Society B, titled “Making gene drive biodegradable.”
Self-deleting genes tested as part of the concept of mosquito population control
15844charlottelarson, NEWYORK NEWS TIMES, 2020-12-28 18:49:28.
Most genetic engineering strategies designed to control mosquito populations, and their ability to spread diseases such as malaria, require gene editing to be combined with gene drives. Gene drives allow altered DNA to spread rapidly throughout the population.
Genetic sexing strains for the population suppression of the mosquito vector Aedes aegypti
15691P. Koskinioti, A. A. Augustinos, D. O. Carvalho, M. Misbah-ul-Haq, G. Pillwax, L. D. d. l. Fuente, G. Salvador-Herranz, R. A. Herrero and K. Bourtzis, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190808. 2020-12-28 15:27:53.
Here, we report on the construction of two genetic sexing strains using red- and white-eye colour mutations as selectable markers. Quality control analysis showed that the Red-eye genetic sexing strains (GSS) is better and more genetically stable than the White-eye GSS. The introduction of an irradiation-induced inversion (Inv35) increases genetic stability and reduces the probability of female contamination of the male release batches. Bi-weekly releases of irradiated males of both the Red-eye GSS and the Red-eye GSS/Inv35 fully suppressed target laboratory cage populations within six and nine weeks, respectively
A patent review on strategies for biological control of mosquito vector
15377K. Parihar, M. Telang and A. Ovhal, World Journal of Microbiology and Biotechnology, 36:23. 2020-12-09 20:28:33.
This paper presents a comprehensive technology overview of patent documents disclosing biological agents for mosquito control. The patent analysis revealed that comparable number of patent documents were filed in two technology categories: non-recombinant agents and genetically modified (GM) agents. In the category of non-recombinant agents, toxic peptides from microbes and biological consortia seemed to be the earliest technology noted right from the year 1965 whereas the patent filings for suppression of mosquito population using genetic modification techniques have emerged from the year 2000 onwards. The United States of America is the leading patent filing jurisdiction followed by China and the Great Britain. Academic institutes have filed higher number of patent applications as compared to private companies. University of Florida was found to be the leading patent filing entity and its patents were focused on suppression of vector population using techniques such as release of insects with dominant lethal (RIDL) and RNA interference (RNAi).
A Gene Drive Could Wipe Out Mosquitoes. But What If We Want To Turn It Off?
15424A. Winkler, freethink, 2020-12-05 15:48:03.
Gene drives are powerful tools: they allow scientists to hack how animals pass down genes to their offspring. They could allow us to wipe out malaria-carrying mosquitoes, preserve endangered species, or fight off crop-eating pests. But once it's out in the wild, a gene drive can't be stopped from spreading — and that makes people nervous. If there are unintended consequences, we want to be able to pull the brakes. Now, UC San Diego researchers have developed a new genetic system that would let scientists halt or neutralize gene drives, even after they are released into the wild. The implications could be huge.
Targeting female flight for genetic control of mosquitoes
15310D. Navarro-Payá, I. Flis, M. A. E. Anderson, P. Hawes, M. Li, O. S. Akbari, S. Basu and L. Alphey, PLOS Neglected Tropical Diseases, 14:e0008876. 2020-12-03 20:11:01.
The yellow fever mosquito and the Southern house mosquito are important vectors of infectious diseases. Given their widespread presence across tropical and subtropical regions of the world and the increased risk of spread due to global warming there is a growing need for population control. Gene drives aim to spread a genetic element within target genes required for mosquito reproduction to disrupt their function and crash a population. Female-specific genes provide interesting candidates for population control since female mosquitoes determine the reproductive capacity of a population as well as being the actual vectors of disease. Here we describe a study on Actin-4 loss in both Aedes aegypti and Culex quinquefasciatus, where we observe female-specific disruption of flight ability and propose it as a candidate for genetic methods of population suppression.
Evaluating Gene Drive Approaches for Public Benefit
15296M. R. Santos, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:14:49.
Gene drive approaches—those which bias inheritance of a genetic element in a population of sexually reproducing organisms—have the potential to provide important public benefits. The spread of selected genetic elements in wild populations of organisms may help address certain challenges, such as transmission of vector-borne human and animal diseases and biodiversity loss due to invasive animals. Adapting various naturally occurring gene drive mechanisms to these aims is a long-standing research area, and recent advances in genetics have made engineering gene drive systems significantly more technically feasible. Gene drive approaches would act through changes in natural environments, thus robust methods to evaluate potential research and use are important.
Modelling the Wolbachia incompatible insect technique: strategies for effective mosquito population elimination
15281D. E. Pagendam, B. J. Trewin, N. Snoad, S. A. Ritchie, A. A. Hoffmann, K. M. Staunton, C. Paton and N. Beebe, BMC Biology, 18:13. 2020-12-02 16:29:23.
We introduce a simple Markov population process model for studying mosquito populations subjected to a Wolbachia-IIT programme which exhibit an unstable equilibrium threshold. The model is used to study, in silico, scenarios that are likely to yield a successful elimination result. Our results suggest that elimination is best achieved by releasing males at rates that adapt to the ever-decreasing wild population, thus reducing the risk of releasing Wolbachia-infected females while reducing costs.
Split drive killer-rescue provides a novel threshold-dependent gene drive
15254M. P. Edgington, T. Harvey-Samuel and L. Alphey, Scientific Reports, 10. 2020-11-25 18:32:01.
Population genetics mathematical models are developed here to demonstrate the threshold-dependent nature of the proposed system and its robustness to imperfect homing, incomplete penetrance of toxins and transgene fitness costs, each of which are of practical significance given that real-world components inevitably have such imperfections. We show that although end-joining repair mechanisms may cause the system to break down, under certain conditions, it should persist over time scales relevant for genetic control programs. The potential of such a system to provide localised population suppression via sex ratio distortion or female-specific lethality is also explored. Additionally, we investigate the effect on introduction thresholds of adding an extra CRISPR base element, showing that this may either increase or decrease dependent on parameter context
Assessment of a Novel Adult Mass-Rearing Cage for Aedes albopictus (Skuse) and Anopheles arabiensis (Patton).
15562H. Maïga, W. Mamai, N. S. Bimbilé Somda, T. Wallner, B. S. Poda, G. Salvador-Herranz, R. Argiles-Herrero, H. Yamada and J. Bouyer, Insects, 11:801. 2020-11-13 15:09:03.
Successful implementation of the sterile insect technique (SIT) against Aedes albopictus and Anopheles arabiensis relies on a continuous supply of sterile males. To meet this requirement, optimization of the mass-rearing techniques is needed. This study, therefore, aims to assess a new mass-rearing cage (MRC) in terms of egg production efficiency and egg hatch rate (quality). In addition, adult survival was evaluated based on a cage adult-index for Ae. albopictus. Moreover, the cage’s suitability for use in mass An. arabiensis egg production was compared to that of the FAO/IAEA Anopheles reference cage. In Ae. albopictus rearing, the new MRC produced 1,112,110 eggs per cage following six blood meals, with minimum loss of eggs in the egging water. Furthermore, the adult index gave a good proxy of daily mortality rates in Ae. albopictus. In An. arabiensis rearing, about 130,000 eggs per egg batch were collected both from the new and the reference MRC. These findings suggest that the new MRC prototype is efficient in terms of egg production and can be used for mass-rearing in SIT programs targeting Ae. albopictus as well as An. arabiensis. The adult index was also positively validated for the detection of unusual mortality rates in Ae. albopictus mass-rearing facilities. Overall, the new MRC has shown several advantages; however, further improvements are necessary to minimize escapes during the egg collection processes
Brave New Planet: Reshaping Nature Through Gene Drives
15047E. Lander, Brave New Planet, 2020-11-09 19:26:24.
A new technology, called gene drives, has the power to spread any genetic instructions you wish across an entire animal or plant species in the wild. It might let us restore ecosystems ravaged by invasive species, or help species adapt to climate change. And, it might save millions of children from dying of malaria. But could altering nature in this way, and on this scale, have unintended consequences? And, when it comes reshaping ecosystems, who needs to say yes?
Gene Drives: A Controversial Tool to Fight Malaria
15008H. Albert, LABIOTECH.eu, 2020-11-09 15:41:52.
The possibility of creating gene drives was introduced into the scientific community in 2003 by Austin Burt, a professor at Imperial College London. Burt was studying ‘selfish genes’ that can copy themselves into a specific target DNA sequence. He suggested that these genes, called homing endonucleases, could be used to make the majority of an organism’s offspring inherit a specific gene, instead of only half of it. This technology has a lot of potential. For example, it could be used to decimate populations of malaria-carrying mosquitoes by making the majority of their offspring male. However, there are concerns about the permanent nature of these genetic modifications and whether it could cause irreparable damage to the ecosystem it is used in.
Genetic engineering and bacterial pathogenesis against the vectorial capacity of mosquitoes
14721M. Qasim, H. M. Xiao, K. He, M. A. A. Omar, F. L. Liu, S. Ahmed and F. Li, Microbial Pathogenesis, 147:8. 2020-10-16 18:16:01.
Here we aimed to focus on the role of bacterial pathogenesis and molecular tactics for the management of mosquitoes and their vectorial capacity.
Mutant mosquitoes: GM insects ‘engineered’ in ‘new approach to pest control’
14337T. Fish, EXPRESS, 2020-09-09 18:44:38.
This cutting-edge research provides the foundations for plans to prevent genetically modified organisms from reproducing with wild organisms.
Genome Editing 2020: Ethics and Human Rights in Germline Editing in Humans and Gene Drives in Mosquitoes
13198G. J. Annas, American Journal of Law and Medicine, 46:143-165. 2020-07-12 18:17:19.
G. J. Annas (2020). American Journal of Law and Medicine. doi: 10.1177/0098858820933492. I begin with a discussion of so far disastrously unsuccessful attempts to regulate germline editing in humans, including a summary of the first application of germline genome editing in humans and its aftermath. I then turn to a discussion of setting ethical standards for a genomic technology that has not yet been deployed in nature—gene drives. Finally, I end by suggesting that human rights can and should be directly applicable to defining the ethics of genomic research.
The need for new vector control approaches targeting outdoor biting anopheline malaria vector communities
12808S. Sougoufara, E. C. Ottih and F. Tripet, Parasites & Vectors, 13:15. 2020-06-10 19:48:24.
Since the implementation of Roll Back Malaria, the widespread use of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) is thought to have played a major part in the decrease in mortality and morbidity achieved in malaria-endemic regions. In the past decade, resistance to major classes of insecticides recommended for public health has spread across many malaria vector populations. Increasingly, malaria vectors are also showing changes in vector behaviour in response to current indoor chemical vector control interventions. Changes in the time of biting and proportion of indoor biting of major vectors, as well as changes in the species composition of mosquito communities threaten the progress made to control malaria transmission. Outdoor biting mosquito populations contribute to malaria transmission in many parts of sub-Saharan Africa and pose new challenges as they cannot be reliably monitored or controlled using conventional tools. Here, we review existing and novel approaches that may be used to target outdoor communities of malaria vectors. We conclude that scalable tools designed specifically for the control and monitoring of outdoor biting and resting malaria vectors with increasingly complex and dynamic responses to intensifying malaria control interventions are urgently needed. These are crucial for integrated vector management programmes designed to challenge current and future vector populations.
Modeling confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit Aedes aegypti populations
11548H. M. Sánchez C, J. B. Bennett, S. L. Wu, G. Rašić, O. S. Akbari and J. M. Marshall, BMC Biology, 18:50. 2020-05-12 14:50:48.
Here, we model hypothetical releases of two recently engineered threshold-dependent gene drive systems—reciprocal chromosomal translocations and a form of toxin-antidote-based underdominance known as UDMEL—to explore their ability to be confined and remediated.
Guidance Framework for Testing the Sterile Insect Technique as a Vector Control Tool against Aedes-Borne Diseases
12451WHO & IAEA, WHO & IAEA, 2020-04-23 20:31:06.
This document is intended to be a comprehensive guide for programme managers tasked with recommending a “go/no-go” decision on testing, full deployment and scale-up of the sterile insect technique (SIT) in regions of the world affected by diseases transmitted by Aedes mosquitoes. However, the authors hope that the material presented herein will be used more widely—by scientists, decision makers, review groups and others.
Opinions of key stakeholders on alternative interventions for malaria control and elimination in Tanzania
11461M. F. Finda, N. Christofides, J. Lezaun, B. Tarimo, P. Chaki, A. H. Kelly, N. Kapologwe, P. Kazyoba, B. Emidi and F. O. Okumu, Malaria Journal, 19:164. 2020-04-23 15:13:29.
Malaria control in Tanzania currently relies primarily on long-lasting insecticidal nets and indoor residual spraying, alongside effective case management and behaviour change communication. This study explored opinions of key stakeholders on the national progress towards malaria elimination, the potential of currently available vector control interventions in helping achieve elimination by 2030, and the need for alternative interventions that could be used to supplement malaria elimination efforts in Tanzania.
Can we kill the dreaded mosquito? Do we even want to?
11228Stacey McKenna, Sierra, 2020-04-19 15:40:08.
As a major vector for disease, the mosquito has harmed more human beings than just about any other animal, and a changing climate is only boosting those numbers. As the range of disease-carrying species of mosquitoes expands, so does their ability to transmit the parasites and viruses that result in malaria, chikungunya, Zika, yellow fever, West Nile, and dengue fever. In 2018, the continental United States saw a 25 percent increase in severe, neuroinvasive cases of West Nile virus compared with a decade earlier. And over the past three decades, the CDC reports, the worldwide incidence of dengue fever has risen 30-fold.
‘Gene Drive’ to curb malaria raises ethical questions as well
11220Gyanedra Nath Mitra, The Pioneer, 2020-03-25 15:23:14.
A new technology ‘Gene Drive’ for mosquito control is currently confined to the laboratory since it raises an ethical question, if such a technology could in future be misused to the detriment of humanity.
Should the humans be allowed to genetically modify insects?
11222Olivia Abbe, NYK Daily, 2020-03-24 15:27:57.
Genetic engineering, also called Genetic modification or Genetic manipulation, is the direct manipulation of an organism’s genes using biotechnology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesising the DNA.
Public health concerns over gene-drive mosquitoes: will future use of gene-drive snails for schistosomiasis control gain increased level of community acceptance?
7950D. O. Famakinde, Pathogens and Global Health, 2020-02-26 20:49:43.
With the advent of CRISPR (clustered regularly interspaced short palindromic repeat)-based gene drive, present genetic research in schistosomiasis vector control envisages the breeding and release of transgenic schistosome-resistant (TSR) snail vectors to curb the spread of the disease. Although this approach is still in its infancy, studies focussing on production of genetically modified (GM) mosquitoes (including gene-drive mosquitoes) are well advanced and set the pace for other transgenic vector research. Unfortunately, as with other GM mosquitoes, open field release of gene-drive mosquitoes is currently challenged in part by some concerns such as gene drive failure and increased transmission potential for other mosquito-borne diseases among others, which might have adverse effects on human wellbeing. Therefore, not only should we learn from the GM mosquito protocols, frameworks and guidelines but also appraise the applicability of its current hurdles to other transgenic vector systems, such as the TSR snail approach. Placing these issues in a coherent comparative perspective, I argue that although the use of TSR snails may face similar technical, democratic and diplomatic challenges, some of the concerns over gene-drive mosquitoes may not apply to gene-drive snails, proposing a theory that community consent will be no harder and possibly easier to obtain for TSR snails than the experience with GM mosquitoes. In the future, these observations may help public health practitioners and policy makers in effective communication with communities on issues regarding the use of TSR snails to interrupt schistosomiasis transmission, especially in sub-Saharan Africa.
The Buzz About Genetically Modified Mosquitoes – a podcast
7932The Scientist Creative Services Team, The Scientist, podcast. 2020-02-26 18:17:44.
Mosquito-borne diseases afflict a large portion of the world. In this month’s episode, we consider genetic methods to eradicate diseases such as Zika fever, Dengue fever, and malaria. We spoke with Omar Akbari, professor of Cell and Developmental Biology at the University of California, San Diego, to learn more.
Vector genetics, insecticide resistance and gene drives: an agent-based modeling approach to evaluate malaria transmission and elimination
7941P. Selvaraj, E. A. Wenger, D. Bridenbecker, N. Windbichler, J. R. Russell, J. Gerardin, C. A. Bever and M. Nikolov, bioRxiv, 2020.01.27.920421. 2020-02-06 20:32:18.
Vector control has been a key component in the fight against malaria for decades, and chemical insecticides are critical to the success of vector control programs worldwide. However, increasing resistance to insecticides threatens to undermine these efforts. Understanding the evolution and propagation of resistance is thus imperative to mitigating loss of intervention effectiveness. Additionally, accelerated research and development of new tools that can be deployed alongside existing vector control strategies is key to eradicating malaria in the near future. Methods such as gene drives that aim to genetically modify large mosquito populations in the wild to either render them refractory to malaria or impair their reproduction may prove invaluable tools. Mathematical models of gene flow in populations can offer invaluable insight into the behavior and potential impact of gene drives as well as the spread of insecticide resistance in the wild. Here, we present the first multi-locus, agent-based model of vector genetics that accounts for mutations and many-to-many mappings of genotypes to phenotypes to investigate gene flow and the propagation of gene drives in Anopheline populations. This model is embedded within a large scale individual-based model of malaria transmission representative of a high burden, high transmission setting characteristic of the Sahel. Results are presented for the selection of insecticide-resistant vectors and the spread of resistance through repeated deployment of insecticide treated nets (ITNs), in addition to scenarios where gene drives act in concert with existing vector control tools such as ITNs. The roles of seasonality, spatial distribution of vector habitat and feed sites, and existing vector control in propagating alleles that confer phenotypic traits via gene drives that result in reduced transmission are explored. The ability to model a spectrum of vector species with different genotypes and phenotypes in the context of malaria transmission allows us to test deployment strategies for existing interventions that reduce the deleterious effects of resistance and allows exploration of the impact of new tools being proposed or developed.Author summary Vector control interventions are essential to the success of global malaria control and elimination efforts but increasing insecticide resistance worldwide threatens to derail these efforts. Releasing genetically modified mosquitoes that use gene drives to pass on desired genes and their associated phenotypic traits to the entire population within a few generations has been proposed to address resistance and other issues such as transmission heterogeneity that can sustain malaria transmission indefinitely. While the ethics and safety of these methods are being debated, mathematical models offer an efficient way of predicting the behavior and estimating the efficacy of these interventions if deployed to specific regions facing challenges to reaching elimination. We have developed a detailed mathematical model of vector genetics where specific genomes code for physical attributes that influence transmission and are affected by the surrounding environment. This is the first model to incorporate an individual-based multi locus genetic model into a detailed individual-based model of malaria transmission. This model opens the door to investigate a number of subtle but important questions such as the effects of small numbers of mosquitoes in a region sustaining malaria transmission during the low transmission season, and the success of gene drives in regions where extant vector control interventions could kill off gene drive mosquitoes before establishment. Here, we investigate the reduced efficacy of current vector control measures in the presence of insecticide resistance and evaluate the likelihood of achieving local malaria elimination using gene drive mosquitoes released into a high transmission setting alongside other vector control measures.
Disrupting female flight in the vector Aedes aegypti
5624O'Leary, S. and Z. N. Adelman, bioRxiv, 862300:862300. 2019-12-17 16:35:43.
Aedes aegypti is a vector of dengue, chikungunya, and Zika viruses. Current vector control strategies such as community engagement, source reduction, and insecticides have not been sufficient to prevent viral outbreaks. Thus, interest in novel strategies involving genetic engineering is growing. Female mosquitoes rely on flight to mate with males and obtain a bloodmeal from a host. We hypothesized that knockout of genes specifically expressed in female mosquitoes associated with the indirect flight muscles would result in a flightless female mosquito. With the CRISPR-Cas9 system, we performed embryonic microinjections of Cas9 protein and guide RNAs specific to genes hypothesized to control flight in mosquitoes, and have obtained genetic knockouts in several genes specifically expressed in the flight-muscle, including those specific to female flight muscle. Analysis of the phenotype of these female-specific gene knockout mutants resulted in flightless females and flying males. While further assessment is required, this work lays the groundwork for a mechanism of population control that is female-specific for the Ae. aegypti vector.
Genetic Control of Mosquitoes
5588Alphey, L., Annual Review of Entomology, 59:205-224. 2019-12-16 19:01:55.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their properties, especially between self-limiting strategies, where the modification has limited persistence, and self-sustaining strategies, which are intended to persist indefinitely in the target population and may invade other populations. Several methods with different molecular biology are under development and the first field trials have been completed successfully.
Out for blood: the fight against the planet’s deadliest creature
5681Matsangou, E., The New Economy, 2019-12-02 19:16:40.
The deadliest creature on the planet is not a great white shark, a starved lion, an enraged hippopotamus or a poisonous snake – it’s the minute mosquito. According to the World Health Organisation (WHO), mosquitoes kill millions of people each year, with malaria – the most deadly mosquito-borne disease – responsible for more than half of these fatalities. The Bill and Melinda Gates Foundation has noted: “Malaria’s economic impact is estimated to cost billions of dollars in lost productivity every year.”
A Controversial Swarm Of Genetically Modified Mosquitoes In A Lab In Italy
5527NPR, 2019-10-20 19:41:57.
An international team of scientists is conducting a controversial experiment in Italy. The experiment is designed to test genetically modified mosquitoes that researchers hope could provide a powerful new weapon to fight malaria, which remains one of the world's greatest scourges.
Dit Afrikaanse dorp krijgt, als eerste plek ter wereld, gentechmuggen tegen malaria
5676Boersma, Hidde, de Volkskrant, 2019-09-09 19:06:00.
Dit Afrikaanse dorp krijgt, als eerste plek ter wereld, gentechmuggen tegen malaria
Gene drive mosquitoes and the new era of medical colonialism
4536Mayet, MC, L. I.; Sirinathsingji, E, GM Watch, 2019-01-22 00:00:00.
The highly contentious issue of gene drive technologies – a novel extreme form of genetic engineering designed to alter or even eradicate entire populations and species – was at the heart of the international negotiations at the biennial UN Biodiversity Conference held in Sharm el-Sheikh, Egypt, in November 2018.
Male competition and the evolution of mating and ire-history traits in experimental populations of Aedes aegypti
3939Qureshi, AA, A.; Hollis, B.; Ponlawat, A.; Cator, L. J., Proceedings of the Royal Society B-Biological Sciences, 286:20190591. 2019-01-17 00:00:00.
Aedes aegypti is an important disease vector and a major target of reproductive control efforts. We manipulated the opportunity for sexual selection in populations of Ae. aegypti by controlling the number of males competing for a single female. Populations exposed to higher levels of male competition rapidly evolved higher male competitive mating success relative to populations evolved in the absence of competition, with an evolutionary response visible atter only five generations. We also detected correlated evolution in other important mating and life-history traits, such as acoustic signalling, fecundity and body size. Our results indicate that there is ample segregating variation for determinants of male mating competitiveness in wild populations and that increased male mating success trades-off with other important life-history traits. The mating conditions imposed on laboratory-reared mosquitoes are likely a significant determinant of male mating success in populations destined for release.
Population genetics of Anopheles funestus, the African malaria vector, Kenya
3936Ogola, EOO, J. O.; Mwangangi, J. M.; Masiga, D. K.; Tchouassi, D. P., Parasites & Vectors, 12:15. 2019-01-14 00:00:00.
Anopheles funestus is among the major malaria vectors in Kenya and sub-Saharan Africa and has been recently implicated in persistent malaria transmission. However, its ecology and genetic diversity remain poorly understood in Kenya.MethodsUsing 16 microsatellite loci, we examined the genetic structure of An. funestus sampled from 11 locations (n = 426 individuals) across a wide geographical range in Kenya spanning coastal, western and Rift Valley areas.ResultsKenyan An. funestus resolved as three genetically distinct clusters. The largest cluster (FUN1) broadly included samples from western and Rift Valley areas of Kenya with two clusters identified from coastal Kenya (FUN2 and FUN3), not previously reported. Geographical distance had no effect on population differentiation of An. funestus. We found a significant variation in the mean Plasmodium infectivity between the clusters ((2) = 12.1, df = 2, P = 0.002) and proportional to the malaria prevalence in the different risk zones of Kenya. Notably, there was variation in estimated effective population sizes between the clusters, suggesting possible differential impact of anti-vector interventions in represented areas.ConclusionsHeterogeneity among Kenyan populations of An. funestus will impact malaria vector control with practical implications for the development of gene-drive technologies. The difference in Plasmodium infectivity and effective population size between the clusters could suggest potential variation in phenotypic characteristics relating to competence or insecticide resistance. This is worth examining in future studies.
CRISPR in Parasitology: Not Exactly Cut and Dried!
3894Bryant, JMB, S.; Glover, L.; Hutchinson, S.; Rachidi, N., Trends in Parasitology, 35:409-422. 2019-01-12 00:00:00.
CRISPR/Cas9 technology has been developing rapidly in the field of parasitology, allowing for the dissection of molecular processes with unprecedented efficiency. Optimization and implementation of a new technology like CRISPR, especially in nonmodel organisms, requires communication and collaboration throughout the field. Recently, a 'CRISPR in Parasitology' symposium was held at the Institut Pasteur Paris, bringing together scientists studying Leishmania, Plasmodium, Trypanosoma, and Anopheles. Here we share technological advances and challenges in using CRISPR/Cas9 in the parasite and vector systems that were discussed. As CRISPR/Cas9 continues to be applied to diverse parasite systems, the community should now focus on improvement and standardization of the technique as well as expanding the CRISPR toolkit to include Cas9 alternatives/derivatives for more advanced applications like genome-wide functional screens.
Modelling the potential of genetic control of malaria mosquitoes at national scale
3933North, ARB, Austin; Godfray, H. Charles J., BMC Biology, 17:26. 2019-01-11 00:00:00.
The persistence of malaria in large parts of sub-Saharan Africa has motivated the development of novel tools to complement existing control programmes, including gene-drive technologies to modify mosquito vector populations. Here, we use a stochastic simulation model to explore the potential of using a driving-Y chromosome to suppress vector populations in a 106 km2 area of West Africa including all of Burkina Faso.
A Question of Consent: Exterminator Mosquitoes in Burkina Faso
5538ETC group, 2019-01-08 20:10:07.
Target Malaria’s planned release of GMO mosquitos is step toward release of gene drive mosquitoes, a high-risk technology aimed at the elimination of entire species. Hundreds of organizations have demanded a moratorium on the use of this technology outside of strictly-controlled laboratories.
Large-cage assessment of a transgenic sex-ratio distortion strain on populations of an African malaria vector
3910Facchinelli, LN, A.; Collins, C.; Menichelli, M.; Persampieri, T.; Bucci, A.; Spaccapelo, R.; Crisanti, A.; Benedict, M., Parasites & Vectors, 12:70. 2019-01-08 00:00:00.
Novel transgenic mosquito control methods require progressively more realistic evaluation. The goal of this study was to determine the effect of a transgene that causes a male-bias sex ratio on Anopheles gambiae target populations in large insectary cages. Life history characteristics of Anopheles gambiae wild type and Ag(PMB)1 (aka (gfp)124L-2) transgenic mosquitoes, whose progeny are 95% male, were measured in order to parameterize predictive population models. Ag(PMB)1 males were then introduced at two ratios into large insectary cages containing target wild type populations with stable age distributions and densities. The predicted proportion of females and those observed in the large cages were compared. A related model was then used to predict effects of male releases on wild mosquitoes in a west African village. The frequency of transgenic mosquitoes in target populations reached an average of 0.44 +/- 0.02 and 0.56 +/- 0.02 after 6 weeks in the 1:1 and in the 3:1 release ratio treatments (transgenic male:wild male) respectively. Transgenic males caused sex-ratio distortion of 73% and 80% males in the 1:1 and 3:1 treatments, respectively. The number of eggs laid in the transgenic treatments declined as the experiment progressed, with a steeper decline in the 3:1 than in the 1:1 releases. The results of the experiment are partially consistent with predictions of the model; effect size and variability did not conform to the model in two out of three trials, effect size was over-estimated by the model and variability was greater than anticipated, possibly because of sampling effects in restocking. The model estimating the effects of hypothetical releases on the mosquito population of a West African village demonstrated that releases could significantly reduce the number of females in the wild population. The interval of releases is not expected to have a strong effect. The biological data produced to parameterize the model, the model itself, and the results of the experiments are components of a system to evaluate and predict the performance of transgenic mosquitoes. Together these suggest that the Ag(PMB)1 strain has the potential to be useful for reversible population suppression while this novel field develops.
The Release of Genetically Engineered Mosquitoes in Burkina Faso: Bioeconomy of Science, Public Engagement and Trust in Medicine
3890Beisel, UG, J. K., African Studies Review, 62:164-173. 2019-01-08 00:00:00.
Malaria, which is transmitted by mosquitoes, continues to be responsible for a significant number of disease episodes and childhood deaths on the African continent. A variety of mosquito control strategies are currently inplace, but since case numbers are rising again, and drug and insecticide tolerance slow down progress made, there has been a push for innovative strategies. In August 2018, the National Biosafety Agency of Burkina Faso granted approval for the release of a maximum of 10,000 male Anopheles mosquitoes in experimental trials conducted by the multi-country consortium Target Malaria. These mosquitoes are rendered infertile through genetic modification, namely through “re-programming” of endonucleases that “cut through essential genes,” in this case, genes for fertility (Target Malaria 2019). The idea is that through the sterilization of male mosquitoes, the population of malaria-transmitting mosquitoes will be reduced, thereby decreasing the overall number of malaria infections.
Modeling the mutation and reversal of engineered underdominance gene drives
3909Edgington, MPA, Luke S., Journal of Theoretical Biology, 479:14-21. 2019-01-07 00:00:00.
A range of gene drive systems have been proposed that are predicted to increase their frequency and that of associated desirable genetic material even if they confer a fitness cost on individuals carrying them. Engineered underdominance (UD) is such a system and, in one version, is based on the introduction of two independently segregating transgenic constructs each carrying a lethal gene, a suppressor for the lethal at the other locus and a desirable genetic “cargo”. Under this system individuals carrying at least one copy of each construct (or no copies of either) are viable whilst those that possess just one of the transgenic constructs are non-viable. Previous theoretical work has explored various properties of these systems, concluding that they should persist indefinitely in absence of resistance or mutation. Here we study a population genetics model of UD gene drive that relaxes past assumptions by allowing for loss-of-function mutations in each introduced gene. We demonstrate that mutations are likely to cause UD systems to break down, eventually resulting in the elimination of introduced transgenes. We then go on to investigate the potential of releasing “free suppressor” carrying individuals as a new method for reversing UD gene drives and compare this to the release of wild-types; the only previously proposed reversal strategy for UD. This reveals that while free suppressor carrying individuals may represent an inexpensive reversal strategy due to extremely small release requirements, they are not able to return a fully wild-type population as rapidly as the release of wild-types.
Gene drive for population genetic control: non-functional resistance and parental effects
3888Beaghton, AKH, Andrew; Nolan, Tony; Crisanti, Andrea; Burt, Austin, Proceedings of the Royal Society B: Biological Sciences, 286:20191586. 2019-01-06 00:00:00.
Gene drive is a natural process of biased inheritance that, in principle, could be used to control pest and vector populations. As with any form of pest control, attention should be paid to the possibility of resistance evolving. For nuclease-based gene drive aimed at suppressing a population, resistance could arise by changes in the target sequence that maintain function, and various strategies have been proposed to reduce the likelihood that such alleles arise. Even if these strategies are successful, it is almost inevitable that alleles will arise at the target site that are resistant to the drive but do not restore function, and the impact of such sequences on the dynamics of control has been little studied. We use population genetic modelling of a strategy targeting a female fertility gene to demonstrate that such alleles may be expected to accumulate, and thereby reduce the reproductive load on the population, if nuclease expression per se causes substantial heterozygote fitness effects or if parental (especially paternal) deposition of nuclease either reduces offspring fitness or affects the genotype of their germline. All these phenomena have been observed in synthetic drive constructs. It will, therefore, be important to allow for non-functional resistance alleles in predicting the dynamics of constructs in cage populations and the impacts of any field release.
Construction of an efficient genomic editing system with CRISPR/Cas9 in the vector mosquito Aedes albopictus
3926Liu, TY, W. Q.; Xie, Y. G.; Liu, P. W.; Xie, L. H.; Lin, F.; Li, C. Y.; Gu, J. B.; Wu, K.; Yan, G. Y.; Chen, X. G., Insect Science, 26:1045-1054. 2019-01-04 00:00:00.
Aedes (Stegomyia) albopictus, also known as the Asian tiger mosquito, is a mosquito which originated in Asia. In recent years, it has become increasingly rampant throughout the world. This mosquito can transmit several arboviruses, including dengue, Zika and chikungunya viruses, and is considered a public health threat. Despite the urgent need of genome engineering to analyze specific gene functions, progress in genetical manipulation of Ae. albopictus has been slow due to a lack of efficient methods and genetic markers. In the present study, we established targeted disruptions in two genes, kynurenine hydroxylase (kh) and dopachrome conversion enzyme (yellow), to analyze the feasibility of generating visible phenotypes with genome editing by the clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated protein 9 (Cas9) system in Ae. albopictus. Following Cas9 single guide RNA ribonucleoprotein injection into the posterior end of pre-blastoderm embryos, 30%-50% of fertile survivors produced alleles that failed to complement existing kh and yellow mutations. Complete eye and body pigmentation defects were readily observed in G1 pupae and adults, indicating successful generation of highly heritable mutations. We conclude that the CRISPR/Cas9-mediated gene editing system can be used in Ae. albopictus and that it can be adopted as an efficient tool for genome-scale analysis and biological study.
Alternative strategies for mosquito-borne arbovirus control
3884Achee, NLG, J. P.; Vatandoost, H.; Seixas, G.; Pinto, J.; Ching-Ng, L.; Martins, A. J.; Juntarajumnong, W.; Corbel, V.; Gouagna, C.; David, J. P.; Logan, J. G.; Orsborne, J.; Marois, E.; Devine, G. J.; Vontas, J., PLOS Neglected Tropical Diseases, 13:e0006822. 2019-01-02 00:00:00.
Mosquito-borne virusessuch as Zika, chikungunya, dengue fever, and yellow fever, among othersare of global importance. Although vaccine development for prevention of mosquito-borne arbovirus infections has been a focus, mitigation strategies continue to rely on vector control. However, vector control has failed to prevent recent epidemics and arrest expanding geographic distribution of key arboviruses, such as dengue. As a consequence, there has been increasing necessity to further optimize current strategies within integrated approaches and advance development of alternative, innovative strategies for the control of mosquito-borne arboviruses. Methods and findings This review, intended as a general overview, is one of a series being generated by the Worldwide Insecticide resistance Network (WIN). The alternative strategies discussed reflect those that are currently under evaluation for public health value by the World Health Organization (WHO) and represent strategies of focus by globally recognized public health stakeholders as potential insecticide resistance (IR)-mitigating strategies. Conditions where these alternative strategies could offer greatest public health value in consideration of mitigating IR will be dependent on the anticipated mechanism of action. Arguably, the most pressing need for endorsement of the strategies described here will be the epidemiological evidence of a public health impact. Conclusions As the burden of mosquito-borne arboviruses, predominately those transmitted by Aedes aegypti and A. albopictus, continues to grow at a global scale, new vector-control tools and integrated strategies will be required to meet public health demands. Decisions regarding implementation of alternative strategies will depend on key ecoepidemiological parameters that each is intended to optimally impact toward driving down arbovirus transmission. Author summary International public health workers are challenged by the burden of arthropod-borne viral diseases, to include mosquito-borne arboviruses transmitted by Aedes aegypti and A. albopictus due in part to lack of sustainable vector control and insecticide resistance (IR), as well as the inability to scale up and sustain existing interventions for prevention of urban epidemics. As a consequence, there has been increasing interest to advance the development of alternative methods. This review provides a general overview of alternative vector-control strategies under development for the control of arbovirus mosquito vectors and highlights how each could offer innovative public health value. Considerations to regulations, acceptance, and sustainability are also provided.
CRISPR Gene Drive (Complete guide 2019)
5507Every Cell A Universe, 2018-11-18 18:59:09.
Crispr gene drive - malaria cure and a new way to look at conservation.
Ecological effects on underdominance threshold drives for vector control
16267D. Khamis, C. El Mouden, K. Kura and M. B. Bonsall, Journal of Theoretical Biology, 456:1-15. 2018-11-07 16:39:27.
Here, ecological and epidemiological dynamics are coupled to a model of mosquito genetics to investigate theoretically the impact of different types of underdominance gene drive on disease prevalence. We model systems with two engineered alleles carried either on the same pair of chromosomes at the same locus or homozygously on different pairs at different loci, genetic lethality that affects both sexes or only females, and bi-sex or male-only releases.
Why is this African village letting mosquitoes in?
4711BBC, BBC, 2018-10-19 00:00:00.
This is a BBC spot about the first release of genetically modified mosquitoes in Africa by the Target Malaria team. Very little information about gene drive but the context of this spot is notable.
Gene drive used to turn all female mosquitos sterile
4589Timmer, J, ARS Technica, 2018-09-27 00:00:00.
We've known for a long time that we can limit malaria infections by controlling the mosquitos that transmit them. But that knowledge hasn't translated into control efforts that have always been completely successful. Many of the approaches we've used to control mosquitos have caused environmental problems, and mosquito populations are large enough that they have evolved resistance to many of our pesticides.; ; That made the development of what are called "gene drive" constructs exciting (if a bit scary). They have the potential to rapidly spread genes throughout a population—including a mosquito population. But the prospect of a modern genetic control of mosquito populations has run up against the very old problem of evolution, as the gene drives often stall due to genetic changes that allow mosquito populations to escape their impact.
Malaria mosquitoes wiped out in lab trials of gene drive testing
4568Kelland, K, The Wire, 2018-09-26 00:00:00.
London: Scientists have succeeded in wiping out a population of caged mosquitoes in laboratory experiments using a type of genetic engineering known as a gene drive, which spread a modification blocking female reproduction.; ; The researchers, whose work was published on Monday in the journal Nature Biotechnology, managed to eliminate the population in less than 11 generations, suggesting the technique could in future be used to control the spread of malaria, a parasitic disease carried by Anopheles gambiae mosquitoes.
Gene drives breakthrough needs urgent restraint
4586Steinbrecher, R, GMWatch, 2018-09-24 00:00:00.
Gene drive researchers associated with Target Malaria and funded by US DARPA, the GATES Foundation and the UK BBSRC have just managed to crash a population of caged mosquitoes after 7-11 generations.(1); ; This is a first, and it has brought this technology beyond the proof of principle. However, in their effort to avoid any resistance to the gene drive, they have focused on a highly stable, ‘conserved’ and vital gene that is found in many species, especially closely related mosquito species. This could enable the gene drive to eliminate populations of multiple non-target species, with very serious implications indeed for biodiversity and ecosystems.; ; We begin by explaining something about gene drives before focusing on what is different about this latest research just published by Kyrou et al. 2018 in Nature Biotechnology.
Here’s the Plan to End Malaria With Crispr-Edited Mosquitoes
4571Molteni, M, Wired, 2018-09-24 00:00:00.
In 2003, scientists at London’s Imperial College hatched a somewhat out-there idea. They wanted to deal with the increasingly pesticide-resistant mosquitoes that were killing half a million people a year by spreading malaria in sub-Saharan Africa. What biologists Austin Burt and Andrea Crisanti proposed was nothing short of hacking the laws of heredity.; ; By planting a deadly gene in mosquito DNA, and engineering it such that the modification would spread through each generation faster than nature intended, they figured they could completely crash a population with just a few Trojan skeeters. This concept of a “gene drive” was decades-old, but no one had successfully concocted one in a lab, let alone applied it to a global public health scourge.
For the first time, researchers will release genetically engineered mosquitoes in Africa
11444Ike Swetitz, STAT, 2018-09-05 18:02:01.
The government of Burkina Faso granted scientists permission to release genetically engineered mosquitoes anytime this year or next, researchers announced Wednesday. It’s a key step in the broader efforts to use bioengineering to eliminate malaria in the region.
Gene drive to reduce malaria transmission in sub-Saharan Africa
3963Burt, AC, Mamadou; Crisanti, Andrea; Diabate, Abdoulaye; Kayondo, Jonathan K., Journal of Responsible Innovation, 5:S66-S80. 2018-01-21 00:00:00.
Despite impressive progress, malaria continues to impose a substantial burden of mortality and morbidity, particularly in sub-Saharan Africa, and new tools will be needed to achieve elimination. Gene drive is a natural process by which some genes are inherited at a greater-than-Mendelian rate and can spread through a population even if they cause harm to the organisms carrying them. Many different synthetic gene drive systems have been proposed to suppress the number of mosquitoes and/or reduce vector competence. As with any control measure, due attention should be paid to the possible evolution of resistance. No gene drive construct has yet been reported that is "field-ready" for release, and when such constructs are developed, they should be assessed on a case-by-case basis. Gene drive approaches to vector control promise to have a number of key features that motivate their continued development, and scrutiny, by all concerned.
Population seasonality and release timing significantly affect the probability of establishment for small releases of gene drive mosquitoes
4001Nikolov, MO, A. L.; Beaghton, A. K.; Beaghton, P. J.; Wenger, E. A.; Burt, A.; Welkhoff, P. A., American Journal of Tropical Medicine and Hygiene, 99:367-367. 2018-01-19 00:00:00.
Highly efficient CRISPR/Cas9 gene-drive systems have recently been developed, targeting reproductive-capacity and malaria-competency loci of malaria transmitting vector species, such as An. gambiae. The resulting drive systems aim to either suppress the local wild-type population or alter its genome, conveying desirable phenotypes such as P. falciparum refractoriness. The potential for sustained spread of gene drive constructs as proposed for malaria and a variety of other applications (pest control, tick borne diseases, dengue) has raised concerns for unintentional or unauthorized organism release outside approved and strictly-regulated trial sites. Previous analyses posit that as few as one or two gene drive organisms carrying efficient gene drive cassettes may establish a permanent (sub)population of genetically-modified (GM) mosquitoes with probability >50%. While these results are broad and cautionary, we show that seasonality is a fundamental environmental characteristic to consider when modeling decision variables. For the first time, we investigate the impact of gene-drive release timing and numbers on the establishment probability of GM vectors in the context of realistic seasonal population variation. We model a male sex bias, driving-Y population suppression gene drive, targeting An. gambiae, since these are among the first field trials candidate constructs. We analyze gene-drive establishment in geographies of different seasonality and spatial vector population features. We show that releasing a small number of gene-drive mosquitoes over the few weeks in the beginning of the wet season facilitates population founder effects and high establishment probability: between 60% - 80% for releases of as few as one or two mosquitoes. However, releasing genedrive mosquitoes outside this time results in much lower establishment probability, typically <20%. Our findings address crucial ethical and environmental concerns, which may guide whether, how, and where to set up gene-drive trials.
Identifying and detecting potentially adverse ecological outcomes associated with the release of gene-drive modified organisms
3980Hayes, KRH, G. R.; Dana, G. V.; Foster, S. D.; Ford, J. H.; Thresher, R.; Ickowicz, A.; Peel, D.; Tizard, M.; De Barro, P.; Strive, T.; Dambacher, J. M., Journal of Responsible Innovation, 5:S139-S158. 2018-01-18 00:00:00.
Synthetic gene drives could provide new solutions to a range of old problems such as controlling vector-borne diseases, agricultural pests and invasive species. In this paper, we outline methods to identify hazards and detect potentially adverse ecological outcomes at the individual (genotype, phenotype), population, community and ecosystem level, when progressing Gene Drive Modified Organisms through a phased test and release pathway. We discuss the strengths and weaknesses of checklists and structured hazard analysis techniques, identify methods to help meet some of the challenges of detecting adverse ecological outcomes in experiments and confined field trials, and discuss ways to improve the efficiency and statistical rigour of post-release monitoring strategies.
A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes
3987Kyrou, KH, Andrew M.; Galizi, Roberto; Kranjc, Nace; Burt, Austin; Beaghton, Andrea K.; Nolan, Tony; Crisanti, Andrea, Nature Biotechnology, 36:1062–1066. 2018-01-05 00:00:00.
In the human malaria vector Anopheles gambiae, the gene doublesex (Agdsx) encodes two alternatively spliced transcripts, dsx-female (AgdsxF) and dsx-male (AgdsxM), that control differentiation of the two sexes. The female transcript, unlike the male, contains an exon (exon 5) whose sequence is highly conserved in all Anopheles mosquitoes so far analyzed. We found that CRISPR–Cas9-targeted disruption of the intron 4–exon 5 boundary aimed at blocking the formation of functional AgdsxF did not affect male development or fertility, whereas females homozygous for the disrupted allele showed an intersex phenotype and complete sterility. A CRISPR–Cas9 gene drive construct targeting this same sequence spread rapidly in caged mosquitoes, reaching 100% prevalence within 7–11 generations while progressively reducing egg production to the point of total population collapse. Owing to functional constraint of the target sequence, no selection of alleles resistant to the gene drive occurred in these laboratory experiments. Cas9-resistant variants arose in each generation at the target site but did not block the spread of the drive.
Gene drive for Malaria control | Andrea Crisanti |
5519TEDx, 2017-04-04 19:23:37.
Andrea discusses his team's laboratory work that has developed a revolutionary technology to spread genetic modifications from few laboratory mosquitoes to wild populations to eradicate malaria in the near future
Driving out malaria
4598Nolan, TC, A., Scientist, 2017-01-01 00:00:00.
In recent years, researchers have sequenced the genomes of several Anopheles mosquito species, including those responsible for nearly all of the malaria transmission in Africa. With this information, they have begun to identify the genes underlying the insects’ ability to colonize human habitats, their reproductive biology, and their susceptibility to infection by the malaria parasite (Plasmodium spp.). If we know the genes, or variants of genes, that are responsible for key mosquito traits, such as parasite clearance or egg laying, we can theoretically introduce a genetic modification into the insects that reduces malaria transmission.
Using Gene Drive to Control Malaria
4718The Scientist, The Scientist, 2016-12-31 00:00:00.
This article provides illustrations for how gene drive works, how gene drives spread, and how gene drive could be used to control malaria using population-wide gene knockout, skewed sex ratio, and population-wide gene knock-in techniques. Visit the article to view all illustrations.
Gene silencing and gene drive in dengue vector control
4095Paulraj, MGI, S.; Reegan, A. D., Indian Journal of Natural Products and Resources, 7:193-200. 2016-01-13 00:00:00.
Vector-borne diseases are the most feared diseases throughout the world. Mosquitoes are the prime human disease vectors as they are responsible for nearly one million human deaths every year. So they are declared as the most dangerous insects to mankind. Aedes aegypti and Ae. albopictus are the most significant mosquito species, because of their role in transmitting dengue virus. These blood feeding ectoparasites of man and other vertebrates have developed excellent adaptations to survive and multiply in and around human habitations. Chemical-based mosquito control method does not give good results due to rapid development of pesticide resistance in mosquitoes. The past four decades have witnessed the development of several alternate mosquito control methods. Genetic control technologies have been recently developed as efficient and ecofriendly methods. Inundate release of genetically modified mosquitoes with lethal or pathogen-resistant genes for population reduction is a recent technology in mosquito control programme. Recent developments in molecular and genome editing technologies have made it easy to produce thousands of transgenic mosquitoes for field release. The present review highlights various scientific reports and research findings on gene silencing and gene drive techniques in dengue mosquito control.
Back to the future: the sterile insect technique against mosquito disease vectors
25916R. S. Lees, J. R. L. Gilles, J. Hendrichs, M. J. B. Vreysen and K. Bourtzis, Current Opinion in Insect Science, 10:156-162. 2015-06-03 13:09:41.
With the global burden of mosquito-borne diseases increasing, and some conventional vector control tools losing effectiveness, the sterile insect technique (SIT) is a potential new tool in the arsenal. Equipment and protocols have been developed and validated for efficient mass-rearing, irradiation and release of Aedines and Anophelines that could be useful for several control approaches. Assessment of male quality is becoming more sophisticated, and several groups are well advanced in pilot site selection and population surveillance. It will not be long before SIT feasibility has been evaluated in various settings. Until perfect sexing mechanisms exist, combination of Wolbachia-induced phenotypes, such as cytoplasmic incompatibility and pathogen interference, and irradiation may prove to be the safest solution for population suppression.
Genetic Control of Mosquitoes.
5597Alphey, L., Annual Review of Entomology, 59:205-224. 2014-12-17 15:50:24.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their properties, especially between self-limiting strategies, where the modification has limited persistence, and self-sustaining strategies, which are intended to persist indefinitely in the target population and may invade other populations. Several methods with different molecular biology are under development and the first field trials have been completed successfully.
A synthetic homing endonuclease-based gene drive system in the human malaria mosquito
4211Windbichler, NM, M.; Papathanos, P. A.; Thyme, S. B.; Li, H.; Ulge, U. Y.; Hovde, B. T.; Baker, D.; Monnat, R. J.; Burt, A.; Crisanti, A., Nature, 473:212-215. 2011-01-09 00:00:00.
Genetic methods of manipulating or eradicating disease vector populations have long been discussed as an attractive alternative to existing control measures because of their potential advantages in terms of effectiveness and species specificity(1-3). The development of genetically engineered malaria-resistant mosquitoes has shown, as a proof of principle, the possibility of targeting the mosquito's ability to serve as a disease vector(4-7). The translation of these achievements into control measures requires an effective technology to spread a genetic modification from laboratory mosquitoes to field populations(8). We have suggested previously that homing endonuclease genes (HEGs), a class of simple selfish genetic elements, could be exploited for this purpose(9). Here we demonstrate that a synthetic genetic element, consisting of mosquito regulatory regions(10) and the homing endonuclease gene I-SceI(11-13), can substantially increase its transmission to the progeny in transgenic mosquitoes of the human malaria vector Anopheles gambiae. We show that the I-SceI element is able to invade receptive mosquito cage populations rapidly, validating mathematical models for the transmission dynamics of HEGs. Molecular analyses confirm that expression of I-SceI in the male germline induces high rates of site-specific chromosomal cleavage and gene conversion, which results in the gain of the I-SceI gene, and underlies the observed genetic drive. These findings demonstrate a new mechanism by which genetic control measures can be implemented. Our results also show in principle how sequence-specific genetic drive elements like HEGs could be used to take the step from the genetic engineering of individuals to the genetic engineering of populations.
Ethical, legal and social aspects of the approach in Sudan
25823B. B. El Sayed, C. A. Malcolm, A. Babiker, E. M. Malik, M. A. H. El Tayeb, N. S. Saeed, A. H. D. Nugud and B. G. J. Knols, Malaria Journal, 8:S3. 2009-11-16 10:10:31.
The global malaria situation, especially in Africa, and the problems frequently encountered in chemical control of vectors such as insecticide resistance, emphasize the urgency of research, development and implementation of new vector control technologies that are applicable at regional and local levels. The successful application of the sterile insect technique (SIT) for the control of the New World screwworm Cochliomyia hominivorax and several species of fruit flies has given impetus to the use of this method for suppression or elimination of malaria vectors in some areas of Africa including Northern State of Sudan. The research and development phase of the Northern State feasibility study has been started. Sudanese stakeholders are working side-by-side with the International Atomic Energy Agency in the activities of this important phase. Several ethical, legal and social issues associated with this approach arose during this phase of the project. They need to be seriously considered and handled with care. In this paper, these issues are described, and the current and proposed activities to overcome potential hurdles to ensure success of the project are listed.
Spatial and temporal distribution of the malaria mosquito Anopheles arabiensis in northern Sudan: influence of environmental factors and implications for vector control
25826T. B. Ageep, J. Cox, M. M. Hassan, B. G. J. Knols, M. Q. Benedict, C. A. Malcolm, A. Babiker and B. B. El Sayed, Malaria Journal, 8:14. 2009-06-09 10:20:40.
Background: Malaria is an important public health problem in northern Sudan, but little is known about the dynamics of its transmission. Given the characteristic low densities of Anopheles arabiensis and the difficult terrain in this area, future vector control strategies are likely to be based on area-wide integrated pest management (AW-IPM) that may include the sterile insect technique ( SIT). To support the planning and implementation of future AW-IPM activities, larval surveys were carried out to provide key data on spatial and seasonal dynamics of local vector populations. Methods: Monthly cross-sectional larval surveys were carried out between March 2005 and May 2007 in two localities (Dongola and Merowe) adjacent to the river Nile. A stratified random sampling strategy based on the use of Remote Sensing (RS), Geographical Information Systems (GIS) and the Global Positioning System (GPS) was used to select survey locations. Breeding sites were mapped using GPS and data on larval density and breeding site characteristics were recorded using handheld computers. Bivariate and multivariate logistic regression models were used to identify breeding site characteristics associated with increased risk of presence of larvae. Seasonal patterns in the proportion of breeding sites positive for larvae were compared visually to contemporaneous data on climate and river height. Results: Of a total of 3,349 aquatic habitats sampled, 321 (9.6%) contained An. arabiensis larvae. The frequency with which larvae were found varied markedly by habitat type. Although most positive sites were associated with temporary standing water around the margins of the main Nile channel, larvae were also found at brickworks and in areas of leaking pipes and canals-often far from the river. Close to the Nile channel, a distinct seasonal pattern in larval populations was evident and appeared to be linked to the rise and fall of the river level. These patterns were not evident in vector populations breeding in artificial water sources away from the river. Conclusion: The GIS-based survey strategy developed in this study provides key data on the population dynamics of An. arabiensis in Northern State. Quantitative estimates of the contributions of various habitat types and their proximity to settlements provide a basis for planning a strategy for reducing malaria risk by elimination of the vector population.
Deployment of innovative genetic vector control strategies: progress on regulatory and biosafety aspects, capacity building and development of best-practice guidance
4220Beech, CV, S.S.; Quinlan, M.M.; Capurro, Margareth L.; Alphey, L.; Bayard, V.; Bouare, M.; McLeod, M.C.; Kittayapong, P.; Lavery, J.; Lim, L.H.; Marrelli, M.T.; Nagaraju, J.; Ombongi, K.; Othman, R.Y.; Pillai, V.; Ramsey, J.; Reuben, R.; Rose, R.I.; Tyagi, B.K.; Mumford, J., AsPac J. Mol. Biol. Biotechnol., 17:75-85. 2009-01-18 00:00:00.
In the ongoing fight against vectors of human diseases, disease endemic countries (DECs) may soon benefit from innovative control strategies involving modified insect vectors. For instance, three promising methods (viz. RIDL® [Release of Insects with a Dominant Lethal], Wolbachia infection, and refractory mosquito technology) are being developed by researchers around the world to combat Aedes aegypti, the primary mosquito vector of viral fevers such as dengue (serotypes 1–4), chikungunya and yellow fever. Some of these techniques are already being extended to other vectors such as Aedes albopictus (the secondary vector of these diseases) and Anopheles mosquito species that transmit malaria. To enable DECs to take advantage of these promising methods, initiatives are underway that relate to biosafety, risk assessment and management, and ethical–social–cultural (ESC) aspects to consider prior to and during the possible deployment of these technologies as part of an integrated vector control programme. This is a brief overview of the objectives and timelines of some of the initiatives being championed by international institutions, including the United Nations Development Programme (UNDP), the World Health Organization (WHO) and the Grand Challenges in Global Health (GCGH) initiative co-sponsored by the Bill & Melinda Gates Foundation.
Researchers eliminate mosquito population through CRISPR gene editing technology
4566Goss, L, Pharmafile, 2008-09-27 00:00:00.
Researchers at Imperial College London have been able to wipe out a population of mosquitoes through ‘gene drive’ technology. The study, published in the journal Nature Biotechnology saw a CRISPR edited gene being used to prevent female mosquitos from being born.; ; As such after eight generations, an entirely male population had been born, which was then unable to breed. The technology may now be used to block the reproductive capabilities of mosquitoes in the real world, in order to prevent the transmission of malaria.
Towards a sterile insect technique field release of Anopheles arabiensis mosquitoes in Sudan: Irradiation, transportation, and field cage experimentation
25755M. E. H. Helinski, M. M. Hassan, W. M. El-Motasim, C. A. Malcolm, B. G. J. Knols and B. El-Sayed, Malaria Journal, 7:10. 2008-04-25 10:09:22.
Background: The work described in this article forms part of a study to suppress a population of the malaria vector Anopheles arabiensis in Northern State, Sudan, with the Sterile Insect Technique. No data have previously been collected on the irradiation and transportation of anopheline mosquitoes in Africa, and the first series of attempts to do this in Sudan are reported here. In addition, experiments in a large field cage under near-natural conditions are described. Methods: Mosquitoes were irradiated in Khartoum and transported as adults by air to the field site earmarked for future releases (400 km from the laboratory). The field cage was prepared for experiments by creating resting sites with favourable conditions. The mating and survival of (irradiated) laboratory males and field-collected males was studied in the field cage, and two small-scale competition experiments were performed. Results: Minor problems were experienced with the irradiation of insects, mostly associated with the absence of a rearing facility in close proximity to the irradiation source. The small-scale transportation of adult mosquitoes to the release site resulted in minimal mortality (< 6%). Experiments in the field cage showed that mating occurred in high frequencies (i.e. an average of 60% insemination of females after one or two nights of mating), and laboratory reared males (i.e. sixty generations) were able to inseminate wild females at rates comparable to wild males. Based on wing length data, there was no size preference of males for mates. Survival of mosquitoes from the cage, based on recapture after mating, was satisfactory and approximately 60% of the insects were recaptured after one night. Only limited information on male competitiveness was obtained due to problems associated with individual egg laying of small numbers of wild females. Conclusion: It is concluded that although conditions are challenging, there are no major obstacles associated with the small-scale irradiation and transportation of insects in the current setting. The field cage is suitable for experiments and studies to test the competitiveness of irradiated males can be pursued. The scaling up of procedures to accommodate much larger numbers of insects needed for a release is the next challenge and recommendations to further implementation of this genetic control strategy are presented.
Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae
4247Windbichler, NP, P. A.; Crisanti, A., PLOS Genetics, 4:1-9. 2008-01-05 00:00:00.
We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome-carrying spermatozoa. Notably, these male mosquitoes also induced complete early dominant embryo lethality in crosses with wild-type females. Morphological and molecular data indicated that all spermatozoa, irrespectively of the inheritance of the transgene, carried a substantial amount of I-PpoI protein that could attack the maternally inherited chromosome X of the embryo. Besides the obvious implications for implementing vector control measures, our data demonstrated the feasibility of generating synthetic sex distorters and revealed the intriguing possibility of manipulating maternally inherited genes using wild-type sperm cells carrying engineered endonucleases.
Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos
4259Windbichler, NP, P. A.; Catteruccia, F.; Ranson, H.; Burt, A.; Crisanti, A., Nucleic Acids Research, 35:5922-5933. 2007-01-17 00:00:00.
Homing endonuclease genes (HEGs) are selfish genetic elements that combine the capability to selectively disrupt specific gene sequences with the ability to rapidly spread from a few individuals to an entire population through homologous recombination repair events. Because of these properties, HEGs are regarded as promising candidates to transfer genetic modifications from engineered laboratory mosquitoes to wild-type populations including Anopheles gambiae the vector of human malaria. Here we show that I-SceI and I-PpoI homing endonucleases cleave their recognition sites with high efficiency inA. gambiae cells and embryos and we demonstrate HEG-induced homologous and non-homologous repair events in a variety of functional assays. We also propose a gene drive system for mosquitoes that is based on our finding that I-PpoI cuts genomic rDNA located on the X chromosome in A. gambiae, which could be used to selectively incapacitate X-carrying spermatozoa thereby imposing a severe male-biased sex ratio.
Meiotic drive by the Y-linked D gene in Aedes aegypti (L.) (Diptera : Culicidae) is associated with disruption of spermiogenesis, leading to premature senescence of spermatozoa
4253Owusu-Daaku, KOB, R. D.; Wood, R. J., Arthropod Structure & Development, 36:233-243. 2007-01-11 00:00:00.
Y chromosome meiotic drive in the mosquito Aedes aegypti, due to the gene D (Distorter) in coupling with M (male determination) [the MD haplotype], is associated with spermiogenic disruption, leading to senescence, at a rate Proportionate to male excess. Spermiogenesis was compared between 'Enhanced Mutant' males with a strongly female-depleted sex ratio (8.9% females), 'Mutant' males showing a lesser degree of distortion (38.3% females), and two controls with normal sex ratios (51.2% and 49.2% females). Sections of testes dissected front mature pupae and adults aged 0, 4, 8, 12 and 16 days were examined by transmission electron microscopy. A difference between Mutant and control spermiogenesis was apparent as early as the pupal stage when some Mutant spermatids showed extra tail elements (axonemes and/or mitochondrial derivatives). The same was true of Enhanced Mutant males but to a more extreme degree. Sperm senescence was evident in Enhanced Mutant testes from day 0 of adult life but in Mutant testes not until day 4. Progressive disorganisation was associated with many loose organelles, and disturbance of the anterior-posterior axis of gamete differentiation within the testis. Degenerative changes of a similar kind in the controls did not become apparent until day 8. These findings are discussed with respect to other characteristics of this meiotic drive system, in terms of a theory of inhibition of reduction division in spermatogenesis associated with fragmentation of the X chromosome, leading to the formation of a restitution nucleus as early as rnetaphase 1. (c) 2007 Elsevier Ltd. All rights reserved.
A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila
4248Chen, CHH, H. X.; Ward, C. M.; Su, J. T.; Schaeffer, L. V.; Guo, M.; Hay, B. A., Science, 316:597-600. 2007-01-06 00:00:00.
One proposed strategy for controlling the transmission of insect-borne pathogens uses a drive mechanism to ensure the rapid spread of transgenes conferring disease refractoriness throughout wild populations. Here, we report the creation of maternal-effect selfish genetic elements in Drosophila that drive population replacement and are resistant to recombination-mediated dissociation of drive and disease refractoriness functions. These selfish elements use microRNA-mediated silencing of a maternally expressed gene essential for embryogenesis, which is coupled with early zygotic expression of a rescuing transgene.
The Sterile Insect Technique: can established technology beat malaria?
25843M. E. H. Helinski, B. El-Sayed and B. G. J. Knols, Entomologische Berichten, 66:13-20. 2006-06-06 14:48:37.
The Sterile Insect Technique (SIT) is the mass production, sterilisation and subsequent release of sterile insects into a target population in an area-wide integrated approach. The released sterile males mate with wild females; they thus no longer produce offspring and therefore the size of the target population is reduced. Over the years, SIT has proven to be a safe, effective and environmentally sound method to suppress, eliminate or contain pest populations. The International Atomic Energy Agency (IAEA) has a long history of supporting SIT programmes against key insect pests, including fruit flies, tsetse flies and moths. Recently, an integrated five year study to assess the feasibility of SIT to control African malaria mosquitoes has been initiated. In this article, we discuss the components and research requirements for such a feasibility study including sexing, mass production, sterilisation and release methodologies.
Malaria Control with Genetically Manipulated Insect Vectors
16035L. Alphey, C. B. Beard, P. Billingsley, M. Coetzee, A. Crisanti, C. Curtis, P. Eggleston, C. Godfray, J. Hemingway, M. Jacobs-Lorena, A. A. James, F. C. Kafatos, L. G. Mukwaya, M. Paton, J. R. Powell, W. Schneider, T. W. Scott, B. Sina, R. Sinden, S. Sink, Science, 298:119. 2002-10-04 19:49:32.
At a recent workshop, experts discussed the benefits, risks, and research priorities associated with using genetically manipulated insects in the control of vector-borne diseases.
Variation in Y chromosome meiotic drive in Aedes aegypti (Diptera: Culicidae): a potential genetic approach to mosquito control
4387OwusuDaaku, KOW, R. J.; Butler, R. D., Bulletin of Entomological Research, 87:617-623. 1997-01-05 00:00:00.
Reciprocal crosses between strains of Aedes aegypti (Linnaeus) from different geographical areas have revealed an unexpectedly complex pattern of holandrically inherited male biased sex ratios in F2. The variation has been interpreted in terms of a web of X-Y interactions in F1, in which the Y chromosome may or may not show meiotic drive against the X chromosome with which it is paired. The pattern of inheritance is not in agreement with a single form of Y chromosome, driving with different degrees of intensity against Xs of different sensitivity, but indicates different forms of driving Y chromosome. A rule has emerged that if F1 males from any cross give rise to a male distorted sex ratio in their progeny (F2), the males from the reciprocal cross give rise to a normal sex ratio. All eleven newly colonized strains from Ghana showed Y meiotic drive against the Xs of five strains, one of American and four of Australian origin, although one of the eleven showed a greater degree of drive than the other ten against the same sensitive strains. The variation observed is discussed in relation to previous studies on meiotic drive by the MD haplotype, and to the possible exploitation of sex ratio distortion in controlling this potentially dangerous insect.
Combining the meiotic drive gene-D and the translocation T-1 in the mosquito, Aedes aegypti(L) .2: Recombination
4481Pearson, AMW, R. J., Genetica, 54:79-85. 1980-01-19 00:00:00.
Recombination on the sex-chromosome of Aedes aegypti has been studied in male genotypes incorporating the sex-linked translocation T1 and the meiotic drive gene D from three different strains (Trinidad, Bozo and Caracas).
Possible replacement of malaria mosquitoes
6118S. Avery Jones, Transactions of The Royal Society of Tropical Medicine and Hygiene, 51:469-470. 1957-08-10 19:43:41.
Sir,--The purpose of this letter is to draw the attention of research workers in control of mosquito colonies to the possible value of investigating the factors governing the infection of mosquitoes with parasites of human malaria. If a strain of a vector species could be isolated that has inability to become infective as a dominant characteristic, the way would be opened up to implant such mosquitoes in areas where the normal vectors of the same species have been reduced in numbers. There is the hope that they would breed and become locally predominant.
