Keywords: Anopheles
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.
Potential benefits, opportunities, risks and challenges of population suppression gene drive mosquitoes for malaria control described in the scholarly literature: a rapid scoping review
35472Fürer, C. L., Fischer, T. B., Suter, T., Winkler, M. S., and Knoblauch, A. M., Impact Assessment and Project Appraisal, 2026-02-27 18:07:52.
Gene drive mosquitoes represent a promising strategy to alter mosquito populations and reduce disease transmission. However, their use has generated considerable debate due to ecological, ethical, and societal concerns. This paper reviews risks, challenges, benefits, and opportunities of gene drive technology, focusing on environmental, social, economic, and health implications. A literature search of peer-reviewed articles published between January 2019 and September 2023 was conducted using PubMed, Cochrane, Embase (Elsevier), and Google Scholar. Eligible papers included keywords such as ‘gene drive’, ‘mosquitoes’, and ‘Anopheles’. Extracted statements were grouped as ‘risks/challenges’, ‘benefits/opportunities’, or ‘ambivalent’, and classified across five dimensions: environmental/entomological/ecological, social, economic, health, and technological. From 1304 papers identified, 53 were included, yielding 892 statements. Of these, 66.5% addressed ‘risks/challenges’, 26.3% ‘benefits/opportunities’, and 7.2% were ‘ambivalent’. Most statements were classified under the ‘environmental/entomological/ecological’ dimension (46.1%), followed by ‘social’ (24.6%), ‘health’ (18.5%), ‘GM technology’ (7.2%), and ‘economic’ (3.6%). Commonly cited ‘risks/challenges’ included potential off-target effects, fitness costs, and development of resistance. The breadth of identified considerations, alongside the predominantly risk-focused discourse, highlights the need for multidimensional assessments. Early evaluations should integrate biosafety assessments with inclusive frameworks such as Strategic Environmental Assessments (SEA) and Environmental, Social, and Health Impact Assessments (ESHIA) to support responsible deployment.
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.
Assessing the population genetic structure and demographic history of Anopheles gambiae and Anopheles arabiensis at island and mainland sites in Uganda: implications for testing novel malaria vector control approaches
35384Mwima, R., Hui, TY.J., Lukyamuzi, E. et al., Malar J, 2026-01-20 13:40:12.
Despite substantial investments in malaria control, the disease remains a major burden in sub-Saharan Africa, particularly Uganda. Novel tools such as gene drive systems are being developed to suppress malaria vector populations, but their deployment requires detailed knowledge of mosquito population genetics. The genetic structure, diversity, and demographic history of Anopheles gambiae and Anopheles arabiensis were assessed at six sites in Uganda: three islands in Lake Victoria and three mainland sites. A total of 2918 An, gambiae and 173 An. arabiensis were genotyped using targeted amplicon sequencing of 62 loci across coding and non-coding regions of the genome. Population structure analyses revealed clear separation between the two species but little differentiation within each species across sites. Pairwise FST values among An. gambiae populations were low (0.00054–0.028) but often statistically significant, with mainland populations showing higher connectivity and island populations exhibiting greater isolation. Anopheles arabiensis mainland populations showed no statistically significant differentiation, suggesting panmixia. Principal component analysis and Bayesian clustering similarly distinguished species-level structure but no obvious substructure within sites. Mainland An. gambiae populations displayed higher nucleotide diversity than island populations, while An. arabiensis showed the lowest diversity overall. Tajima’s D values were negative across sites, consistent with recent population expansions. Effective population size estimates indicated small populations at the islands (146–249) compared to large mainland populations (4054–8190). These findings demonstrate strong genetic differentiation between An. gambiae and An. arabiensis, and subtle but meaningful structure between island and mainland An. gambiae populations. The reduced diversity and small effective population sizes at island sites suggest stronger genetic drift and limited gene flow, in contrast to the highly connected mainland populations. This study highlights how geographic and ecological factors shape mosquito population structure and provides critical evidence for the design and monitoring of genetic-based vector control interventions, including the planning and evaluation of field trials.
Beyond the static lab: environmental variability in genetically modified mosquito target gene identification for malaria control
35371Luna Dael, Maria L. Simões, Current Opinion in Insect Science, 2026-01-17 15:23:28.
As malaria remains a critical public health challenge causing hundreds of thousands of deaths annually, novel methods to combat it are urgently needed. Genetically modified mosquitoes (GMMs) offer a promising innovative approach to reduce malaria transmission. However, the foundational research to identify the target gene candidates for genetic modification is typically conducted under static laboratory conditions. These standardized insectary settings of constant temperature and humidity do not reflect the dynamic environmental and climatic variability that mosquitoes and the pathogens they carry encounter in nature. This review argues that this “lab-to-field” discrepancy represents a significant knowledge gap. We highlight that natural variations in environmental factors influence Anopheles and Plasmodium biology, and mosquito innate immunity responses, with consequences for vector competence and malaria transmission. Insufficient consideration of environmental variability during the initial gene discovery phase risks developing GMMs where the intended function of the genetic modification may be compromised by environmental stress. We emphasize the need to incorporate realistic environmental variability into the upstream GMM development, particularly in the face of escalating climate change.
The symbiotic Wolbachia in Anopheles and its role in reducing the transmission of Plasmodium: updates and prospects
35359Nehra, R., Dhanda, S., Singh, K. et al., Archives of Microbiology, 208. 2026-01-14 11:49:05.
Reducing malaria transmission and the prospects for vector control include multi-pronged strategies, such as interrupting the parasite cycle in both vectors and mosquitoes. Effective vector control remains essential to prevent malaria transmission. This is all the more important as problems such as resistance to insecticides and the lack of a highly effective malaria vaccine remain. New generation vector control measures and optimised products are essential to address the public health needs for malaria eradication. Strategies to reduce malaria transmission include the use of insecticide-treated nets (ITNs), indoor residual spraying (IRS) and other measures. Recent studies have shown that Wolbachia pipientis, a bacterium that acts as an intracellular endosymbiotic in host cells, is becoming increasingly popular as a new method of control for Anopheles mosquitoes, both for cytoplasmic incompatibility and for pathogen blocking. Anopheles gambiae, the infection rate ranged from 8 to 24% in the wild population of the same study in the case of An. coulzzi (WAnga) in Ghana, with a prevalence of 4%. Various studies have successfully identified Wolbachia in several species of Anopheles. A highly infected Anopheles species A population in the Democratic Republic of the Congo (DRC) showed a 91% infection rate (strain wAnsA). Broader surveys list additional species hosting natural Wolbachia, including An. funestus, An. moucheti, An. melas, An. nili, An. coustani, An. dirus, An. baimaii, An. hyrcanus, and An. sinensis, among others, totalling around 31 Anopheles species. In Anopheles stephensi, researchers achieved stable maternal transmission of the wPip strain with a 100% infection frequency in the transinfected line across generations. The infection caused nearly complete cytoplasmic incompatibility (CI) and moderate fitness costs. Previous experimental infections using the wAlbB strain in An. stephensi similarly established CI and partial protection against Plasmodium infection. Wolbachia has been detected naturally at low prevalence (~ 1.4%) in field-collected An. culicifacies samples in India. However, these infections are often rare and may not lead to a high blocking effect of the pathogens. Despite the notable progress in demonstrating the CI and moderate inhibitory effect of the pathogen in several Anopheles trans-infected lines, the remaining setbacks include persistent, mother-transmitted infection with a high population replacement or suppression potential that will be relevant for widespread use. This comprehensive evaluation identified the need for further research on host-symbiotic interactions, improved genetic engineering tools and comprehensive long-term field evaluations to fully realise the potential of Wolbachia as a vector control tool for malaria.
Wolbachia for malaria control
35347Zhang, Xinmi et al., Trends in Parasitology, 2026-01-08 10:34:56.
Malaria remains a major public health concern, and traditional vector control methods face growing challenges, underscoring the need for novel strategies. The success of Wolbachia-based dengue control, together with the establishment of Plasmodium-blocking Wolbachia transinfections in Anopheles, highlights the potential of a new tool for malaria control. This review discusses the main experimental systems for studying Wolbachia–Anopheles interactions, emphasizing the challenges of generating Wolbachia transinfected Anopheles gambiae strains. Experiments utilizing Plasmodium parasite challenge in transiently and stably infected Anopheles demonstrated that Wolbachia-induced Plasmodium suppression is feasible. Building on insights from Wolbachia–Aedes–arborvirus systems – and with current evidence from Anopheles systems – we also address mechanisms of Plasmodium suppression. Finally, we outline challenges and opportunities for translating these findings from proof-of-concept to field application.
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 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.
Suitability of a chilled environmental box of the Precision X-RAD 320 cabinet style irradiator for the irradiation of mosquitoes and tsetse in the context of the sterile insect technique
35276Hanano Yamada, Bénéwendé Aristide Kaboré, Samar Eisa, et al., Journal of Economic Entomology, 2025-11-03 11:17:02.
A cabinet-style small animal X-irradiator outfitted with an environmental chamber which can provide a consistent, chilled environment during irradiation was tested to sterilize the human and animal disease vectors Aedes aegypti Linnaeus (Diptera: Culicidae), Anopheles arabiensis Patton (Diptera: Culicidae), Glossina palpalis gambiensis Vanderplank (Diptera: Glossinidae) in the frame of the sterile insect technique (SIT). The environmental chamber enables the irradiation of immobilized, compacted adult insects avoiding mechanical damage incurred by movement and, thereby, maintaining better insect quality. For the species tested, there was no significant difference in dose response when irradiating late-stage pupae or adults, and chilling at 7 °C did not affect irradiation outcome in terms of sterility induced. The X-irradiator was shown to be effective and suitable for the sterilization of these important target species of the SIT and offers a practical means to sterilize insects at the adult stage which require chilling for immobilization.
The nanosd integral gene drive enables population modification of the malaria vector Anopheles gambiae
35269Pei-Shi Yen, Sebald A N R Verkuijl, Paolo Capriotti, et al., G3 Genes|Genomes|Genetics, 2025-11-02 17:38:52.
The modification of mosquito populations at scale through CRISPR-Cas9-mediated homing gene drives is a promising route for malaria vector control. Integral gene drives (IGDs) are designed to utilise the regulatory sequences of endogenous genes to reduce the size of the modification required for nuclease and effector expression. In this study, we describe the creation and characterisation of the nanosd IGD, which targets and is inserted into the nanos gene of the malaria vector Anopheles gambiae, and show that it achieves high rates of gene drive (98.4% in females, 99.5% in males). We find that homozygous nanosd females but not males show impaired fecundity and exhibit variable degrees of ovary underdevelopment. Transcriptomic analysis of ovaries points to decreased transcript levels of the nanos gene when harbouring Cas9 and changes to other fertility-related genes. As a minimal genetic modification, nanosd does not induce widespread transcriptomic perturbations that would affect vector competence, and we show that its susceptibility to Plasmodium spp. and O’nyong nyong virus infection remains similar to wild-type mosquitoes. Importantly, we find that nanosd propagates efficiently in caged mosquito populations and is maintained as a source of Cas9 after the emergence of drive-resistant alleles, whilst also mobilising a non-autonomous antiparasitic effector modification. The nanosd gene drive shows promise as a genetic tool for malaria vector control via population modification, and we outline steps towards its further optimisation.
A male-drive female-sterile system for the self-limited control of the malaria mosquito Anopheles gambiae
35261Strampelli, A., Willis, K., Gulliford, H.R. et al., Nature Communications, 16. 2025-10-28 08:43:17.
Despite great leaps forward in preventing and treating malaria, several challenges, including insecticide resistance, have hindered progress in fighting the disease. Thus, there is a pressing need for new tools to control malaria, including the use of genetically modified mosquitoes (GMMs) in the field. Various genetic strategies for vector control are currently explored, ranging from self-sustaining GMMs with unrestricted geographic and temporal spread to self-limiting alternatives. Here, we describe 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 show that repeated releases of MDFS can lead to elimination of caged mosquito populations. Based on these findings, modelling suggests MDFS could be a highly effective and self-limiting strategy for suppressing wild malaria mosquito populations.
Engineering gene drive docking sites in a haplolethal locus in Anopheles gambiae
35231Smidler, A.L., Marrogi, E.A., Scott, S. et al., Scientific Reports, 15. 2025-10-09 10:19:39.
Gene drives are selfish genetic elements which promise to be powerful tools in the fight against vector-borne diseases such as malaria. We previously proposed population replacement gene drives designed to better withstand the evolution of resistance by homing through haplolethal loci. Because most mutations in the wild-type allele that would otherwise confer resistance are lethal, only successful drive homing and functional r1 alleles permits the cell to survive. Here we outline the development and characterization of two ΦC31-Recombination mediated cassette exchange gene drive docking lines with these features in Anopheles gambiae, a first step towards construction of robust gene drives in this important malaria vector. We outline adaption of the technique HACK (Homology Assisted CRISPR knockin) to knock-in two docking site sequences into a paired putative haplolethal-haplosufficient (Ribosome–Proteasome) locus, and confirm that these docking lines permit insertion of drive-relevant transgenes. We report the first anopheline proteasome knockouts, and identify ribosome mutants in the process reveal a major lethality and infertility hurdle that such designs must overcome to develop robust drives in the future. Although we do not achieve drive, this work provides a new tool for constructing future evolution-robust drive systems and reveals critical challenges that must be overcome for development of future gene drives designed to target haplolethal loci in anophelines and, potentially, other metazoans.
Estimated cost and operational structure of pgSIT malaria vector control programs in selected West African countries
35203William A.C. Gendron, Robyn Raban, Agastya Mondal, et al., Scientific African, 29. 2025-09-30 15:35:38.
Malaria control has primarily been achieved through vector control, but current methods are insufficient to achieve elimination. Precision guided sterile insect technique (pgSIT) is a mosquito suppression technique that generates sterile male mosquitoes for mass release. Our previous studies showed that this intervention is expected to be highly cost-effective in a malaria endemic region of West Africa, but these estimates used only 15-31% capacity for sex sorting, which is the limiting production step and a primary cost. We, therefore, determined the most cost efficient facility size by calculating the cost per million Anopheles gambiae suppressed as the facility was scaled up to suppress more mosquitoes. We developed an optimized facility size per 9.2 million mosquitoes suppressed, which can be a framework for scaling and increases the cost effectiveness of this intervention. The development of this intervention can potentially interrupt malaria transmission, strengthen local public health institutions, create manufacturing capacity, provide local jobs, and enhance regional health security capabilities that are more resilient to disruptions in supply chains and malaria investment.
Wolbachia Infection in Iranian Malaria Vectors: Prevalence and Biocontrol Implications
35124Shahin Saeedi, Fateh Karimian, Seyed Hassan Moosa-Kazemi, et al., Tropical Medicine & International health, 2025-09-08 08:50:24.
Wolbachia-based vector control is an emerging tool in malaria prevention research. This study evaluates Wolbachia infection in Iranian mosquitoes, focusing on seven known malaria vectors. Mosquitoes were collected from nine provinces of Iran (2016–2019), and Wolbachia infection status was analysed via PCR targeting eight genes: wsp, gatB, ftsZ, dnaA, groEL, gltA, CoxA and fbpA. We examined 1094 specimens from seven malaria vectors (Anopheles stephensi Liston, 1901; Anopheles culicifacies s.l. James, 1901; Anopheles fluviatilis s.l. James, 1902; Anopheles maculipennis s.l. Meigen, 1818; Anopheles sacharovi Favr, 1903; Anopheles dthali Patton, 1905; Anopheles superpictus s.l. Grassi, 1899), four non-malaria vectors (Anopheles mongolensis Linton, Lee and Curtis, 2005; Anopheles hyrcanus Pallas, 1771; Anopheles claviger Meigen, 1804; Anopheles turkhudi Liston, 1901) and three Culex species (Culex pipiens Linnaeus, 1758; Culex perexiguus Theobald, 1903; Culex theileri Theobald, 1903). PCR revealed Wolbachia DNA exclusively in An. dthali and Culex species, with infection rates of 73.4% for An. dthali and 77.78%–96.77% for Culex, notably higher in males. Wolbachia was detected in all regions except one in the north. Phylogenetic analysis revealed Wolbachia strains in An. dthali and Culex belong to supergroup B, closely related to strains in An. moucheti and An. demeilloni. This suggests broader applications for biocontrol strategies. The high Wolbachia prevalence in An. dthali is promising for malaria prevention. Future research should confirm cytoplasmic incompatibility and explore wAdth's potential to block malaria transmission.
Growth and development of two predator species fed a diet of genetically engineered mosquitoes
35081Egan, C.M., Chamberland, L., Ditter, R.E. et al., Parasites Vectors, 18. 2025-08-28 16:18:12.
Genetically engineered mosquitoes (GEMs) with gene drives have been developed for malaria control but remain untested in natural environments. Upon release, GEMs are expected to modify or replace wild-type counterparts, potentially uniquely interacting with nontarget organisms (NTOs). Concerns exist over possible negative effects on NTOs and broader ecological harm. Predators consuming GEMs represent a group that interacts closely with these modified mosquitoes. Here, we examine the effect of GEM and wild-type Anopheles coluzzii diets on the growth of two predator species: the aquatic mosquitofish (Gambusia affinis) and the terrestrial bold jumping spider (Phidippus audax). Gambusia affinis was fed lyophilized gravid mosquitoes, and growth was measured using length and mass. Phidippus audax was fed live semi-gravid mosquitoes, with growth tracked via eye size, body size, and mass. No adverse effects were found in either predator species fed GEM diets. Gambusia affinis showed no significant growth differences between diet groups. However, P. audax that were fed GEMs consumed more mosquitoes, grew larger, and matured faster. Differences in predator growth rate suggest that GEMs’ nutritional content is similar to that of wild-type mosquitoes, but that they may be more vulnerable to predation. Further research is needed to explore whether GEM visual or behavioral traits increase their susceptibility to predators.
Genetic control strategies for population suppression in the Anopheles gambiae complex: a review of current technologies
35055Alekos Simoni, Ignacio Tolosana, Federica Bernardini, Current Opinion in Insect Science, 2025-08-25 20:42:10.
Malaria continues to pose a critical public health threat, with mosquitoes from the Anopheles gambiae complex acting as the main vectors of the disease in sub-Saharan Africa, where approximately 95% of malaria-related deaths occur. Despite significant advancements in vector control, such as insecticide-treated bed nets and indoor spraying, the effectiveness of these interventions is increasingly compromised by various challenges, including rising levels of insecticide and pathogen resistance, mosquito behavioural adaptations, and persistent funding gaps. In this context, genetic vector control strategies have shown considerable promise, primarily based on findings from controlled laboratory studies. This review explores the development of these genetic approaches within the Anopheles gambiae complex and outlines future directions for their advancement and potential integration into malaria control efforts.
The buzz stops here
35057Bill Gates, Gates Notes, 2025-08-19 20:44:24.
I've been working on malaria for over two decades. I’ve talked with researchers in labs and parents who’ve lost children to a mosquito bite. I’ve seen promising new tools and surprising setbacks. But I’ve rarely been as excited about a new innovation as I am about this one. In a lab in Tanzania, researchers are studying something incredible: a mosquito that can’t give you malaria. It looks and behaves like any other mosquito. It flies, bites, and breeds. But what it doesn’t do is transmit one of the deadliest diseases on the planet—which means it could save hundreds of thousands of lives a year. This mosquito was developed in 2023 by a team of African scientists at the Ifakara Health Institute in partnership with Imperial College London. It’s the first transgenic mosquito ever created on African soil—meaning that scientists have made a small, targeted change to its DNA. It was both a major scientific milestone and a major moment of African leadership in the global health space. The project is called Transmission Zero, and its goal is as ambitious as its name: to eliminate malaria not by killing mosquitoes, but by making them unable to transmit it to humans.
Driving a protective allele of the mosquito FREP1 gene to combat malaria
34980Li, Z., Dong, Y., You, L. et al., Nature, 2025-07-24 09:46:46.
Malaria remains a substantial global health challenge, causing approximately half a million deaths each year1. The mosquito fibrinogen-related protein 1 (FREP1) is required for malaria parasites to infect the midgut epithelium2. The naturally occurring FREP1Q allele has been reported to prevent parasite infection, while supporting essential physiological functions in the mosquito3. Here we generate congenic strains of Anopheles stephensi, edited to carry either the parasite-susceptible FREP1L224 or the putative-refractory FREP1Q224 alleles. The FREP1Q224 allele confers robust resistance to infection by both human and rodent malaria parasites, with negligible fitness costs. The protective FREP1Q224 allele can be efficiently driven into FREP1L224 mosquito populations using a novel linked allelic-drive system that selectively replaces the L224 codon with the parasite-refractory Q224 allele, thereby rendering populations refractory to parasite infection. This antimalaria drive system provides a novel genetic approach to aid in malaria elimination efforts.
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.
CRISPR technologies for the control and study of malaria-transmitting anopheline mosquitoes
34964Smidler, A.L., Akbari, O.S., Parasites Vectors, 18. 2025-07-08 13:44:43.
Malaria is one of the deadliest diseases on the planet, killing approximately 600,000 people annually, and is transmitted by the bite of an anopheline mosquito. Anophelines, and the diseases they transmit, have changed the course of history and the fate of nations, and their successful control promises to end the transmission of malaria. With the advent of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technologies, the study and control of these deadly pests have been revolutionized. As the release of genetically modified anophelines is being considered, here we outline the advances in CRISPR/Cas9 technologies and how they have revolutionized the study of anopheline basic biology and the development of innovative vector control strategies. We outline the major findings of CRISPR-based basic biological research into traits relevant for vector control including, but not limited to, olfaction, chemosensation, neurobiology, and reproduction. Further, we summarize the advancements in CRISPR-based innovative vector control strategies, such as the precision-guided sterile insect technique (pgSIT), inherited female elimination by genetically encoded nucleases to interrupt alleles (IFEGENIA), X-shredder, Y-linked editors, and gene drives. All in all, this review summarizes the basic biological and vector control research undertaken using CRISPR since its advent approximately a decade ago.
Extended time to maturity in Anopheles coluzzii: Implications of late egg hatch for vector control and transgene fitness
34947Emmanuel C. Ottih, Joe M. Roberts, Toby J. A. Bruce, Frédéric Tripet, Medical and Veterinary Entomology, 2025-06-24 10:11:30.
Maintaining fitness is an important consideration when mosquitoes are mass-reared for the deployment of genetic interventions that are designed to suppress populations because released mosquitoes need to compete with wild-type mosquitoes. Late-hatching mosquitoes are more suitable for transportation to remote field sites. Here, we investigated the fitness of late-hatching phenotypes in Anopheles coluzzii. Selected lines of the VK strain (from Burkina Faso) were created through bidirectional selection for early and late hatching, over 20 generations. These were compared with each other and the established Mopti reference strain from Mali, reared in the lab for >16 years. Significant differences in life-history traits were found between Mopti and VK strains but few differences were found between the selected VK lines. Considering that late-hatching VK lines showed no evidence of fitness costs, our results suggest that the late selected VK lines, which start hatching after 4 days, are an alternative option for egg shipment for mass mosquito releases over the well-established Mopti that hatches within 2 days and has lower adult survival.
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.
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).
Applying the Protective Precautionary Principle to the Ethical Use of Gene Drive Technology for Anopheles gambiae Suppression in Malaria Control
34879Nucharee Wongsamut, Journal of Applied Animal Ethics Research, 2025-06-02 18:16:36.
Malaria contributes to poverty and illness, which further hinder productivity and income generation. Therefore, combating malaria is crucial for breaking the vicious cycle of poverty. Genome editing technologies, such as gene drives designed to suppress Anopheles gambiae mosquito populations, the vector for malaria, have emerged as potential tools in this fight. However, a significant ethical question arises: under what conditions is the use of gene drive technology to suppress Anopheles gambiae mosquito populations justified? This article argues that the Protective Precautionary Principle can serve as a suitable framework for morally assessing such cases. Within this framework, the use of gene drive technology for Anopheles gambiae population suppression would be permissible for laboratory research only. This limited scope minimizes the risk of unforeseen negative consequences, particularly for disadvantaged populations who may have fewer resources to protect themselves from such effects.
Assessing the population genetic structure and demographic history of Anopheles gambiae and An. arabiensis at island and mainland populations in Uganda: Implications for testing novel malaria vector control approaches
34868Rita Mwima, Tin-Yu J. Hui, Edward Lukyamuzi, et al, bioRxiv, 2025-05-26 21:26:56.
This study collected 2918 Anopheles gambiae and 173 Anopheles. arabiensis across six populations from both the islands on Lake Victoria and mainland Uganda for amplicon sequencing. Large pairwise FST values were observed between the two species, indicating their divergence. We observed low but often significant FST values between the 6 An. gambiae populations, while between the An. arabiensis mainland populations, FST values were not significant. Principal Component Analysis also revealed strong genetic structure between the two species but did not provide a clear picture between populations within each species. We also found that mainland An. gambiae populations had higher within population genetic diversity than the islands’, while An. arabiensis had the lowest nucleotide diversity. Tajima’s D values were all negative, suggesting a recent population expansion. The islands An. gambiae populations had very low contemporary effective population sizes in the tens and hundreds, as estimated from linkage disequilibrium, while the mainland population sizes were consistently higher, in the thousands.
Unstable laboratory Wolbachia strain w-Anga is negatively correlated with Plasmodium falciparum in wild malaria vectors
34856Estelle, D.L., Jacques, G.E., Issiaka, S. et al., Scientific Reports, 15. 2025-05-26 20:48:59.
Spread of insecticides resistance threatens the control of malaria. In this context, biological control using an endosymbiotic bacterium Wolbachia is being explored as a complementary method for its control. However, for optimal use of this bacterium in biocontrol strategies, it is imperative to characterize it. So, Anopheles gambiae complex mosquitoes were collected, morphologically identified, then blood fed and gravid female mosquitoes oviposited individually. After oviposition, the species of parent was molecularly determined, along with their w-Anga infection status. Additionally, we performed 16SrRNA gene sequencing of w-Anga-positive mosquitoes to determine their phylogeny. Finally, we amplified gene encoding the circumsporozoite protein to determinate their Plasmodium falciparum infection status and assessed the stability of w-Anga transmission of positive females and their offspring. From the results obtained, our w-Anga strains cluster with other Wolbachia Supergroup B strains. However, the prevalence of Plasmodium falciparum infection was lower in Wolbachia-infected females (4.59%) than in those uninfected (22.02%). Furthermore, the transmission frequency of this bacterium in infected Anopheles coluzzii females of the F0 generation to F1 offspring was 10.64% and 16.67% from infected females of the F1 generation to F2 offspring. This study results will serve as preliminary data for the possible use of Wolbachia in malaria control.
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.
An eco-epidemiological model for malaria with Microsporidia MB as bio-control agent
34793Mfangnia CNT, Tonnang HEZ, Tsanou B, Keith Herren J, Modeling Earth Systems and Environment, 11. 2025-04-23 10:24:11.
Microsporidia MB is an endosymbiont which naturally infects Anopheles mosquitoes. Due to its ability to block Plasmodium transmission, it shows potential as a bio-based agent for the control of malaria. Its self-sustainability is promising, as it can spread through both vertical and horizontal transmissions. However, its low prevalence in mosquito populations remains a challenge. We develop an eco-epidemiological mathematical model describing the co-dynamics of Microsporidia MB (within mosquito population) and malaria (within human population). The model is used to assess the potential of Microsporidia MB-infected mosquitoes on the control of malaria infection. The results on the basic reproduction numbers, the stability of the equilibria, and the existence of bifurcations are obtained, providing conditions for the extinction and persistence of MB-infected mosquitoes. We highlight relevant threshold parameters for the elimination and persistence of MB-infected mosquitoes and malaria-infected individuals. Using real data from Kenya, we found that, given a horizontal transmission rate between 0 and 0.5, a minimum vertical rate of 0.55 is required to avoid extinction of MB-infected mosquitoes. The predicted prevalence of MB-infected mosquitoes using transmission rates reported from lab experiments align with the observed low prevalence of MB-infected mosquitoes in the field, thereby validating our model and results. Finally, predictions indicate that increasing MB mosquito infection could effectively control malaria, with target prevalence varying by region: 15% in Highland, 40% on the coast, and 70% in the Lake region. This study offers insights into the use of bio-based vector population replacement solutions to reduce malaria incidence in regions where Microsporidia MB is prevalent.
Challenges in developing a split drive targeting dsx for the genetic control of the invasive malaria vector Anopheles stephensi
34659Larrosa-Godall, M., Ang, J.X.D., Leftwich, P.T. et al., Parasites & Vectors, 18. 2025-03-25 09:18:22.
Anopheles stephensi is a competent malaria vector mainly present in southern Asia and the Arabian Peninsula. Since 2012, it has invaded several countries of eastern Africa, creating an emerging risk of urban transmission. Urgent efforts are required to develop novel and more efficient strategies for targeted vector control. CRISPR/Cas9-based homing gene drives have been proposed as attractive alternative strategies. Gene drives have the potential to spread a desired trait through a population at higher rates than via normal Mendelian inheritance, even in the presence of a fitness cost. Several target genes have been suggested and tested in different mosquito vector species such as Anopheles gambiae and Aedes aegypti. Several promising suppression drives have been developed in An. gambiae that target the sex determination gene doublesex (dsx). In this study, a geographically confineable gene drive system targeting dsx was developed (dsxgRNA). Here, a transgenic line which expresses Cas9 under the control of the endogenous zpg promoter was generated. Separately a transgenic line which expresses a gRNA targeting the female specific exon of dsx was inserted into that same target site. The reproductive fitness of males and females heterozygous and homozygous for this element was determined. A series of experimental crosses was performed to combine the two elements and assess the homing rate of the dsx element in a split drive system. The drive was able to home in a super-Mendelian rate comparable to those obtained by an autonomous drive in this species. Although inheritance rates as high as 99.8% were observed, potentially providing very potent gene drive, dominant effects on male and female fertility were observed, which would be sufficient to hinder spread of such a drive. Molecular analysis indicated that the gRNA expressing insertion disrupted normal splicing of dsx. These results should be considered when proposing the viability of dsx as a target gene for a population suppression gene drives in Anopheles stephensi. Although high homing rates were observed, the fitness defects found in both males and females carrying the transgene would likely prohibit this drive from functioning in the field.
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.
Engineering gene drive docking sites in a haplolethal locus in Anopheles gambiae
34552Andrea L Smidler, Eryney A Marrogi, Sean Scot, et al., bioRxiv, 2025-03-04 11:03:46.
Gene drives are selfish genetic elements which promise to be powerful tools in the fight against vector-borne diseases such as malaria. We previously proposed population replacement gene drives designed to better withstand the evolution of resistance by homing through haplolethal loci. Because most mutations in the wild-type allele that would otherwise confer resistance are lethal, only successful drive homing permits the cell to survive. Here we outline the development and characterization of two ΦC31-Recombination mediated cassette exchange (RMCE) gene drive docking lines with these features in Anopheles gambiae, a first step towards construction of robust gene drives in this important malaria vector. We outline adaption of the technique HACK (Homology Assisted CRISPR knockin) to knock-in two docking site sequences into a paired haplolethal-haplosufficient (Ribosome-Proteasome) locus, and confirm that these docking lines permit insertion of drive-relevant transgenes. We report the first anopheline proteasome knockouts, and identify ribosome mutants that reveal a major hurdle that such designs must overcome to develop robust drives in the future. Although we do not achieve drive, this work provides a new tool for constructing future evolution-robust drive systems and reveals critical challenges that must be overcome for future development of gene drives designed to target haplolethal loci in anophelines and, potentially, other metazoans.
Exploiting venom toxins in paratransgenesis to prevent mosquito-borne disease
34533French, S., Da Silva, R., Storm, J. et al., Parasites & Vectors, 18. 2025-02-21 11:33:53.
Mosquitoes are responsible for the transmission of numerous pathogens, including Plasmodium parasites, arboviruses and filarial worms. They pose a significant risk to public health with over 200 million cases of malaria per annum and approximately 4 billion people at risk of arthropod-borne viruses (arboviruses). Mosquito populations are geographically expanding into temperate regions and their distribution is predicted to continue increasing. Mosquito symbionts, including fungi, bacteria and viruses, have desirable traits for mosquito disease control including spreading horizontally and vertically through mosquito populations and potentially colonising multiple important vector species. Paratransgenesis, genetic modification of mosquito symbionts with effectors to target the pathogen rather than the vector, is a promising strategy to prevent the spread of mosquito-borne diseases. A variety of effectors can be expressed but venom toxins are excellent effector candidates because they are target specific, potent and stable. However, the only toxins to be explored in mosquito paratransgenesis to date are scorpine and mutated phospholipase A2. To enhance the scope, effectiveness and durability of paratransgenesis, an expanded arsenal of effectors is required. This review discusses other potential toxin effectors for future paratransgenesis studies based on prior in vitro and in vivo antiparasitic and antiviral studies and highlights the need for further research and investment in this area. In terms of mosquito-borne diseases, paratransgenesis strategies have been developed to target Plasmodium. We postulate the potential to apply this principle to target arboviruses using antiviral toxin effectors.
Generating sterile Anopheles mosquitoes to combat malaria transmission
34492Xu, X. and Champer, J., Research Communities by Springer Nature, 2025-02-04 17:49:08.
Malaria remains a deadly disease, claiming hundreds of thousands of lives worldwide every year. The primary vectors of malaria are Anopheles mosquitoes, including Anopheles gambiae and Anopheles stephensi. Controlling mosquito populations is crucial for stopping malaria transmission. Gene drive technology represents a promising alternative to traditional chemical-based control methods, offering a species-specific and eco-friendly approach. However, key challenges in developing gene drives include resistance formation due to end-joining repair after Cas9/gRNA cleavage and the fitness costs associated with drive heterozygotes. One of the most successful gene drive designs to date targets the doublesex (dsx) gene in Anopheles gambiae, as reported by Kyrou et al. (2018). The dsx gene plays a crucial role in sex differentiation, with distinct isoforms expressed in males and females. Disrupting the female-specific isoform results in female sterility. Ideally, only homozygous females exhibit sterility due to a male-like intersex phenotype, while male homozygous and heterozygous mosquitoes of both sexes remain fertile. This makes it a suitable target for a suppression gene drive aimed at reducing the number of fertile females and ultimately eliminating the population.
A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae
34215Tolosana, I., Willis, K., Gribble, M. et al., Nature Communications, 16:206. 2025-01-07 09:21:41.
Genetic control – the deliberate introduction of genetic traits to control a pest or vector population – offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings, but hesitancy due to their invasive and persistent nature may delay their implementation. Here, instead, we describe a self-limiting strategy, designed to have geographically and temporally restricted effect, based on a Y chromosome-linked genome editor (YLE). The YLE comprises a CRISPR-Cas9 construct that is always inherited by males yet generates an autosomal dominant mutation that is transmitted to over 90% of the offspring and results in female-specific sterility. To our knowledge, our system represents a pioneering approach in the engineering of the Y chromosome to generate a genetic control strain for mosquitoes. Mathematical modelling shows that this YLE technology is up to seven times more efficient for population suppression than optimal versions of other self-limiting strategies, such as the widely used Sterile Insect Technique or the Release of Insects carrying a Dominant Lethal gene.
Assessing the Efficacy of Gene-Drive Technology in Reducing Malaria Transmission in Sub-Saharan Africa: Current Progress and Future Prospects
33876Bizimana Rukundo T., IAA Journal of Applied Sciences, 12(1):1-5. 2024-12-10 16:43:06.
Malaria continues to pose a significant public health challenge in Sub-Saharan Africa, necessitating innovative solutions to combat its transmission. This review examined the efficacy of gene-drive technology as a novel approach to reducing malaria transmission through genetic modifications of Anopheles mosquitoes. Utilizing a comprehensive literature review and analysis of experimental studies and pilot projects, we assessed the mechanisms of gene drives, including population suppression and replacement strategies. The findings indicated that gene-drive technology has the potential to significantly alter mosquito populations, thereby diminishing the burden of malaria. However, challenges such as ecological concerns, regulatory complexities, and public acceptance must be addressed for successful implementation. The integration of gene drives with existing malaria control measures, collaborative research efforts, and robust ethical governance is crucial for maximizing effectiveness and ensuring sustainable outcomes. Furthermore, monitoring and evaluation systems are essential for assessing the safety and efficacy of gene-drive initiatives. This review underscored the transformative potential of gene-drive technology in malaria prevention, advocating for continued dialogue among stakeholders to navigate the complexities associated with its application in Sub-Saharan Africa.
Stable introduction of Wolbachia wPip into invasive Anopheles stephensi for potential malaria control
32022Yongkang Liang, Julian Liu, et al., PLoS Neglected Tropical Diseases, 2024-10-01 16:23:02.
Recent efforts have successfully utilized the endosymbiotic bacterium Wolbachia to control mosquito-transmitted viral diseases like dengue in multiple countries. However, similar initiatives have been limited in combating malaria, the most devastating and deadly mosquito-borne disease, which claims over half a million lives each year. This is primarily due to the difficulty in establishing a stable, maternally inheritable Wolbachia infection in Anopheles, the mosquito vector responsible for malaria transmission. A significant concern in malaria control is the invasion of the urban malaria vector Anopheles stephensi into Africa, where malaria burden is highest, and over 40% of the population resides in urban areas. Building on the previous breakthrough of establishing Wolbachia strain wAlbB in An. stephensi, the author has now achieved a second stable infection by transferring the wPip strain from Culex pipiens into this mosquito species using embryonic microinjection. The resultant transinfected HP1 line induces nearly complete cytoplasmic incompatibility when crossed with wild mosquitoes, displays robust fitness and male mating competitiveness, and exhibits strong resilience against heat stress. These advantageous traits position the HP1 line as a promising candidate for further development in malaria control.
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.
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.
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.
Curing mosquitoes with genetic approaches for malaria control
30356Mary Kefi, Victor Cardoso-Jaime, Sally A. Saab, George Dimopoulos, Trends in Parasitology, 2024-05-21 19:48:52.
Malaria remains a persistent global public health challenge because of the limitations of current prevention tools. The use of transgenic mosquitoes incapable of transmitting malaria, in conjunction with existing methods, holds promise for achieving elimination of malaria and preventing its reintroduction. In this context, population modification involves the spread of engineered genetic elements through mosquito populations that render them incapable of malaria transmission. Significant progress has been made in this field over the past decade in revealing promising targets, optimizing genetic tools, and facilitating the transition from the laboratory to successful field deployments, which are subject to regulatory scrutiny. This review summarizes recent advances and ongoing challenges in ‘curing’ Anopheles vectors of the malaria parasite.
A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae
30350Ignacio Tolosana, Katie Willis, Austin Burt, Matthew Gribble, Tony Nolan, Andrea Crisanti, Federica Bernardini, bioRxiv, 2024-05-21 18:59:24.
Genetic control – the deliberate introduction of genetic traits to control a pest or vector population – offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings but hesitancy due to their invasive and persistent nature may delay their implementation. Here instead we describe a self-limiting strategy, designed to have geographically and/or temporally restricted effect, based on a Y chromosome-linked genome editor (YLE). The YLE comprises a CRISPR-Cas9 construct that is always inherited by males yet generates an autosomal dominant mutation that is transmitted to over 90% of the offspring and results in female-specific sterility. Males are unaffected. To our knowledge, our system represents the first engineering of the Y chromosome to generate a genetic control strain for mosquitoes. Mathematical modelling shows that this YLE technology is up to 8 times more efficient for population suppression than optimal versions of other self-limiting strategies.
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.
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.
A population modification gene drive targeting both Saglin and Lipophorin impairs Plasmodium transmission in Anopheles mosquitoes
28671Emily I Green, Etienne Jaouen, Dennis Klug, Roenick Proveti Olmo, Amandine Gautier, Stéphanie Blandin, Eric Marois, eLife, 12. 2023-12-06 11:55:36.
Lipophorin is an essential, highly expressed lipid transport protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles coluzzii Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite Plasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmit Plasmodium berghei expressing the P. falciparum circumsporozoite protein to mice. To force the spread of this anti-malarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic gene Saglin and also cleaves wild-type Lipophorin, causing the anti-malarial modified Lipophorin version to replace the wild type and hitch-hike together with the Saglin drive. Although generating drive-resistant alleles and showing instability in its gRNA-encoding multiplex array, the Saglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarial Lipophorin::Sc2A10 allele. This combination is expected to decrease parasite transmission via two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.
Anopheles gambiae on remote islands in the Indian Ocean: origins and prospects for malaria elimination by genetic modification of extant populations
28597Ditter, R.E., Campos, M., Crepeau, M.W. et al., Scientific Reports, 13. 2023-11-29 16:40:50.
The mosquito Anopheles gambiae s.s. is a primary malaria vector throughout sub-Saharan Africa including the islands of the Comoros archipelago (Anjouan, Grande Comore, Mayotte and Mohéli). These islands are located at the northern end of the Mozambique Channel in eastern Africa. Previous studies have shown a relatively high degree of genetic isolation between the Comoros islands and mainland populations of A. gambiae, but the origin of the island populations remains unclear. Here, we analyzed phylogenetic relationships among island and mainland populations using complete mitochondrial genome sequences of individual A. gambiae specimens. This work augments earlier studies based on analysis of the nuclear genome. We investigated the source population of A. gambiae for each island, estimated the number of introductions, when they occurred and explored evidence for contemporary gene flow between island and mainland populations. These studies are relevant to understanding historical patterns in the dispersal of this important malaria vector and provide information critical to assessing their potential for the exploration of genetic-based vector control methods to eliminate this disease. Phylogenetic analysis and haplotype networks were constructed from mitogenome sequences of 258 A. gambiae from the four islands. In addition, 112 individuals from seven countries across sub-Saharan Africa and Madagascar were included to identify potential source populations. Our results suggest that introduction events of A. gambiae into the Comoros archipelago were rare and recent events and support earlier claims that gene flow between the mainland and these islands is limited. This study is concordant with earlier work suggesting the suitability of these oceanic islands as appropriate sites for conducting field trial releases of genetically engineered mosquitoes (GEMs).
Bill Gates Talks Gene Drives, mRNA, and U.S.$40m in Science Funding
28314N. Mlambo, allAfrica, 2023-10-31 08:32:46.
In 2003, the Bill and Melinda Gates Foundation launched the Grand Challenges initiative in order to find scientific solutions to these health challenges. Initially, the initiative focused on 14 scientific challenges including focusing on creating effective single-dose vaccines that can be used soon after birth, discovering drugs and delivery systems that minimise the likelihood of drug-resistant micro-organisms, creating therapies that can cure latent infection, and developing needle-free delivery systems. "We started Grand Challenges with two goals. In a narrow sense, we wanted to spur specific advances we thought could lead to breakthroughs. In 2003, we listed ... priorities like creating therapies that could cure latent TB infection - and supported researchers who had exciting ideas in those areas. In a broader sense, we hoped to inspire more brilliant scientists to share big ideas about transforming health in low-income countries. We hoped to create a scientific community that was supported to sustain R&D (Research and Development) for the benefit of billions of people who had been neglected," said co-chair of the Bill & Melinda Gates Foundation Bill Gates during his opening remarks at the Grand Challenges meeting held in Dakar, Senegal.
Genetically modified mosquitoes will be ready by 2033 – scientists
28096D. Sekayinga, MONITOR, 2023-10-10 07:43:26.
The Uganda Virus Research Institute (UVR[) has announced that genetically modified mosquitoes will be ready within a decade. Gene-drive mosquitoes are among the anti-malarial strategies the government under the Africa Target Malaria project has embarked on since 2016, to reduce the number of malaria deaths in the country. ''If the non -Gene-drive (sterilised) mosquitoes respond positively at every stage. we shall possibly be able to have the Gene-drives 10 years from now," Dr Jonathan Kayondo, one of the researchers, made the revelation during an anti-malarial training for journalists in Kalangala District last week. Dr Kayondo said every level of research will help in information flow, especially in places where research is conducted like the island of Jaana in Bubeke Sub-county in Kalangala District and Nsazi Island in Koome Sub-county. Mukono District. The two islands have high malaria cases. He added that researchers are yet to receive some Ugandan mosquito species whose genes have beenengineered at a laboratory in the USA for trial lease. "Ne are currently looking at developing sterile male mosquitoes that wouldn't be capable offertilising the female anopheles mosquitoes that spread malaria before introducing gene-drives to thecommunity," he said.
Expansions to the MGDrivE suite for simulating the efficacy of novel gene-drive constructs in the control of mosquito-borne diseases
28003J. B. Bennett, S. L. Wu, P. R. Chennuri, K. M. Myles and M. L. Ndeffo-Mbah, BMC Research Notes, 16:258. 2023-10-05 08:39:23.
The MGDrivE (MGDrivE 1 and MGDrivE 2) modeling framework provides a flexible and expansive environment for testing the efficacy of novel gene-drive constructs for the control of mosquito-borne diseases. However, the existing model framework did not previously support several features necessary to simulate some types of intervention strategies. Namely, current MGDrivE versions do not permit modeling of small molecule inducible systems for controlling gene expression in gene drive designs or the inheritance patterns of self-eliminating gene drive mechanisms. Here, we demonstrate a new MGDrivE 2 module that permits the simulation of gene drive strategies incorporating small molecule-inducible systems and self-eliminating gene drive mechanisms. Additionally, we also implemented novel sparsity-aware sampling algorithms for improved computational efficiency in MGDrivE 2 and supplied an analysis and plotting function applicable to the outputs of MGDrivE 1 and MGDrivE 2.
The Gamble: Can Genetically Modified Mosquitoes End Disease?
27985S. Nolen, New York Times, 2023-09-29 08:00:43.
The malaria situation in São Tomé and Príncipe, an African island nation with a population of 200,000, epitomizes the current challenge in the global struggle against the disease. The country is among the world’s least developed, and it has depended on foreign aid to fight malaria. Various campaigns over the past 50 years drove cases down, only to have them resurge worse than ever when the benefactor moved on. Over the past 18 years, with nearly $21 million from the Global Fund to Fight AIDS, Tuberculosis and Malaria, São Tomé has used a package of tools — including insecticide-treated bed nets; new and better drugs; killing larvae in bodies of water; and indoor spraying of homes — to stunning effect. No one has died of malaria here in the past five years. These countries need a way to fight the disease that is permanent and does not require continuous investment. Greg Lanzaro, a molecular geneticist at the University of California, Davis, who leads the malaria team, believes his grouphas that solution. “We’ve been working on this for 30 years, and from the beginning we said, ‘It has to work, but it also has to be inexpensive,and it has to be sustainable,’” he said as he watched the mosquitoes being released in a Santo Antonio park. “And we believewe have it.” But genetic modification is a controversial endeavor. Governments are hesitant, and few in Africa have laws to regulate theuse of the technology. Its risks lie in the unknowns: Could the modified mosquito evolve in some way that has harmfuleffects on the rest of the ecosystem? Could it prompt a dangerous mutation in the malaria parasite, which will find a new way to spread to survive? It is, in essence, the Jurassic Park question: Could meddling in genetic code have catastrophic consequences that no oneanticipates?
Could a new gene-editing technique be a major breakthrough in the battle against malaria?
27888B. Cottam, GEOGRAPHICAL, 2023-09-23 07:58:35.
The idea is that since female mosquitoes typically only mate once, the mass release of the sterile male mosquitoes should prevent wild females from producing future generations. Insect populations can and have already been successfully suppressed by the release of sterilised males that have been irradiated with gamma or x-rays, a technique that was originally trialled in the USA as a way to control agricultural pests such as fruit flies and screwworms. However, that method of sterilisation has a detrimental impact on the fitness of male mosquitoes, which then struggle to compete for mates with the wild males. That’s why sterilisation needs to be done genetically.
Measuring the Impact of Genetic Heterogeneity and Chromosomal Inversions on the Efficacy of CRISPR-Cas9 Gene Drives in Different Strains of Anopheles gambiae
27837Pescod, Poppy Bevivino, Giulia Anthousi, Amalia Shelton, Ruth Shepherd, Josephine Lombardo, Fabrizio Nolan, Tony, The CRISPR Journal, 2023-09-13 09:06:32.
The human malaria vector Anopheles gambiae is becoming increasingly resistant to insecticides, spurring the development of genetic control strategies. CRISPR-Cas9 gene drives can modify a population by creating double-stranded breaks at highly specific targets, triggering copying of the gene drive into the cut site (?homing?), ensuring its inheritance. The DNA repair mechanism responsible requires homology between the donor and recipient chromosomes, presenting challenges for the invasion of laboratory-developed gene drives into wild populations of target species An. gambiae species complex, which show high levels of genome variation. Two gene drives (vas2-5958 and zpg-7280) were introduced into three An. gambiae strains collected across Africa with 5.3?6.6% variation around the target sites, and the effect of this variation on homing was measured. Gene drive homing across different karyotypes of the 2La chromosomal inversion was also assessed. No decrease in gene drive homing was seen despite target site heterology, demonstrating the applicability of gene drives to wild populations.
Buzzing breakthrough: genetic engineering gives mosquito control an upgrade
27841Sivasubbu, Sridhar Scaria, Vinod, The Hindu, 2023-09-10 09:28:26.
Throughout human history, mosquitoes have constantly buzzed in the background of human existence, irritating us with their incessant bites and occasionally wreaking havoc by transmitting deadly diseases. The earliest known mosquitoes from the fossil record date back at least 70 million years, and evidence of mosquito-borne diseases like malaria dates back to Egyptian mummies from 2000 BC. Apart from malaria, which claims the lives of over half a million people every year and infects close to 250 million, mosquitoes serve as vectors for various other diseases. These include dengue, Zika, lymphatic filariasis, and yellow fever. Understandably, our relationship with these tiny, blood-sucking insects has been far from cordial.
A synthetic biology approach to transgene expression
27699P. Leftwich, T. , J. Purcell, C. , M. Anderson, A. E. , R. Fragkoudis, S. Basu, G. Lycett, T. and L. Alphey, bioRxiv, 2023.08.31.555539. 2023-08-31 09:13:32.
The ability to control gene expression is pivotal in genetic engineering and synthetic biology. However, in most non-model and pest insect species, empirical evidence for predictable modulation of gene expression levels is lacking. This knowledge gap is critical for genetic control systems, particularly in mosquitoes, where transgenic methods offer novel routes for pest control. Commonly, the choice of RNA polymerase II promoter (Pol II) is the primary method for controlling gene expression, but the options are limited. To address this, we developed a systematic approach to characterize modifications in translation initiation sequences (TIS) and 3' untranslated regions (UTR) of transgenes, enabling the creation of a toolbox for gene expression modulation in mosquitoes and potentially other insects. The approach demonstrated highly predictable gene expression changes across various cell lines and promoter sequences, representing a significant advancement in mosquito synthetic biology gene expression.Competing Interest StatementThe authors have declared no competing interest.
High-efficiency gene editing in Anopheles sinensis using ReMOT control
27705X.-l. Yang, X. Ling, Q. Sun, P.-p. Qiu, K. Xiang, u.-f. JHong, S.-l. He, J. Chen, X. Ding, H. Hu, Z.-b. He, C. Zhou, B. Chen and L. Qiao, bioRxiv, 2023.08.29.555096. 2023-08-29 09:32:43.
CRISPR/Cas9-mediated gene editing provides an effective method for deciphering the molecular mechanisms underlying mosquito development and mosquito-borne disease transmission, as well as for exploring genetic control strategies. However, delivering the Cas9 ribonucleoprotein complex by embryo injection to produce genetic modifications is challenging, is mostly confined to model mosquitoes and specialized laboratories, and has low editing efficiency. Here, we established an effective Receptor-Mediated Ovary Transduction of Cargo (ReMOT) control method, enabling the introduction of heritable mutations into Anopheles sinensis, the major malaria vector in China and Southeast Asia, via the injection of female adult mosquitoes. Injection of a mixture of P2C-DsRed and saponin resulted in red fluorescence in the ovaries, with a 100% success rate. Using this system, we knocked-out the pigment synthesis genes, Aswhite and Asyellow, using injected wild-type (WT) females mated with WT males, resulting in the highest efficiency of gene editing among mosquitoes under the same mating conditions. Furthermore, the gene-editing efficiency was increased by at least 2.1-fold using injected WT females mated with mutant males. This improved ReMOT control method exhibits high editing efficiency, with important benefits in terms of functional genomics research and genetic control strategies in An. sinensis. Moreover, this represents a convenient method for gene manipulation in laboratories that are unable to perform embryo injection or that lack embryo-injection equipment.Competing Interest StatementThe authors have declared no competing interest.
A recombinant Aspergillus oryzae fungus transmitted from larvae to adults of Anopheles stephensi mosquitoes inhibits malaria parasite oocyst development
27665L. Kianifard, A. M. Rafiqi, O. Akcakir, A. S. I. Aly, P. F. Billingsley and S. Uysal, Scientific Reports, 13:12177. 2023-08-25 06:27:41.
The control of malaria parasite transmission from mosquitoes to humans is hampered by decreasing efficacies of insecticides, development of drug resistance against the last-resort antimalarials, and the absence of effective vaccines. Herein, the anti-plasmodial transmission blocking activity of a recombinant Aspergillus oryzae (A. oryzae-R) fungus strain, which is used in human food industry, was investigated in laboratory-reared Anopheles stephensi mosquitoes. The recombinant fungus strain was genetically modified to secrete two anti-plasmodial effector peptides, MP2 (midgut peptide 2) and EPIP (enolase-plasminogen interaction peptide) peptides. The transstadial transmission of the fungus from larvae to adult mosquitoes was confirmed following inoculation of A. oryzae-R in the water trays used for larval rearing. Secretion of the anti-plasmodial effector peptides inside the mosquito midguts inhibited oocyst formation of P. berghei parasites. These results indicate that A. oryzae can be used as a paratransgenesis model carrying effector proteins to inhibit malaria parasite development in An. stephensi. Further studies are needed to determine if this recombinant fungus can be adapted under natural conditions, with a minimal or no impact on the environment, to target mosquito-borne infectious disease agents inside their vectors.
How genetically modifying mosquitoes could strengthen the world’s war on malaria
27634S. Oliver and J. Raman, The Conversation, 2023-08-18 07:35:58.
Mosquitoes can be genetically modified through two different technologies. The first method, paratransgenesis, involves infecting mosquitoes with bacteria that prevent them from transmitting malaria. This doesn’t harm the mosquito. It is important not to eliminate or harm mosquitoes because they pollinate many plants and are food for animals like bats, birds and reptiles. Scientists are excited about this method following the recent discovery of a bacterium that occurs naturally in mosquitoes’ guts and appears to prevent the malaria parasite from developing inside the mosquito. The second method involves genetically modifying the mosquitoes themselves. This approach centres on gene drives: genetic systems that ensure genes of interest are inherited by all offspring in every generation. There are two types of gene drive. One aims to reduce the vector population size and is known as population suppression. The other aims to prevent the mosquito from transmitting malaria; it is known as population modification.
Single-cell profiling of Anopheles gambiae spermatogenesis defines the onset of meiotic silencing and premeiotic overexpression of the X chromosome
27624N. Page, C. Taxiarchi, D. Tonge, J. Kuburic, E. Chesters, A. Kriezis, K. Kyrou, L. Game, T. Nolan and R. Galizi, Commun Biol, 6:850. 2023-08-15 10:04:13.
Understanding development and genetic regulation in the Anopheles gambiae germline is essential to engineer effective genetic control strategies targeting this malaria mosquito vector. These include targeting the germline to induce sterility or using regulatory sequences to drive transgene expression for applications such as gene drive. However, only very few germline-specific regulatory elements have been characterised with the majority showing leaky expression. This has been shown to considerably reduce the efficiency of current genetic control strategies, which rely on regulatory elements with more tightly restricted spatial and/or temporal expression. Meiotic silencing of the sex chromosomes limits the flexibility of transgene expression to develop effective sex-linked genetic control strategies. Here, we build on our previous study, dissecting gametogenesis into four distinct cell populations, using single-cell RNA sequencing to define eight distinct cell clusters and associated germline cell-types using available marker genes. We reveal overexpression of X-linked genes in a distinct cluster of pre-meiotic cells and document the onset of meiotic silencing of the X chromosome in a subcluster of cells in the latter stages of spermatogenesis. This study provides a comprehensive dataset, characterising the expression of distinct cell types through spermatogenesis and widening the toolkit for genetic control of malaria mosquitoes.
British super mosquitoes being deployed to wipe out malaria from the planet
27622J. Lawton, Daily Star, 2023-08-15 10:00:16.
The Brit-made mosquitoes are all male and carry a special gene to prevent female offspring from surviving into adulthood.Only females bite and spread malaria. Released into the wild Oxitec’s genetically-modified males mate with wild females. All the female offspring then die. Males - which do not bite or spread the disease - survive and go on to mate with other wild females `dramatically’ reducing the world’s mosquito population and the "spread of malaria". according to Gates. Tests have shown the super mozzies pose no risk to the environment or humans. More than one billion have so far been released worldwide with "no negative impacts", Bill wrote in an online blog. In Brazil the Brit buzzers are helping eliminate dengue fever - another mosquito-transmitted disease which kills up to 40,000-a-year. They will be introduced to Djibouti in east Africa next year to stop a rise in the number of malaria cases from 27 in 2012 to 73,000 in 2020.
Genetically modified Brit mosquitoes could stamp out malaria with Bill Gates’ backing
27619K. Williams, Mirror, 2023-08-15 09:49:13.
British super mosquitoes could be deployed worldwide to eradicate malaria. Billionaire Bill Gates is backing the British effort to send the country’s mosquitoes across the world in an effort to stamp out the deadly disease. This would work because the super mozzies, created by UK biotech firm Oxitec, are capable of killing off their disease-ridden rivals that spread the illness responsible for over half a million deaths a year.Oxitec genetically modifies insects to use them as biological insecticides. They work by the British mozzies being entirely male only and they carry a special gene that stops female offspring from surviving into adulthood. This is key because only the females bite and spread malaria. So Oxitec’s all-male mosquitoes are released into the wild and mate with the wild females, whose female offspring all die off. However, the male offspring survive and, unable to bite and spread the disease, go off into the world and mate with other wild females.
Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control Anopheles gambiae the mosquito vector of human malaria
27626A. Qureshi and J. B. Connolly, Malaria Journal, 22:234. 2023-08-14 10:10:18.
Population suppression gene drive is currently being evaluated, including via environmental risk assessment (ERA), for malaria vector control. One such gene drive involves the dsxFCRISPRh transgene encoding (i) hCas9 endonuclease, (ii) T1 guide RNA (gRNA) targeting the doublesex locus, and (iii) DsRed fluorescent marker protein, in genetically-modified mosquitoes (GMMs). Problem formulation, the first stage of ERA, for environmental releases of dsxFCRISPRh previously identified nine potential harms to the environment or health that could occur, should expressed products of the transgene cause allergenicity or toxicity.
A mosquito symbiont takes down malaria
27667A. Taglialegna, Nature Reviews Microbiology, 2023-08-14 06:27:59.
Malaria, a parasitic infection transmitted by Anopheles mosquitoes, is globally prevalent. Control strategies for malaria include insecticides and antiparasitic drugs, which target the mosquito vector or the parasite in the human host, respectively. The effectiveness of these methods can be undermined by resistance; hence, new containment approaches are needed. In this study, Huang et al. discover Delftia tsuruhatensis TC1, a mosquito symbiotic bacterium that inhibits parasite development via the secretion of a small molecul
Baker: New tools can change mosquitoes’ DNA, but should it be done?
27597K. Baker, Fremont News Messenger, 2023-08-09 06:54:53.
Suppose Sauron — or perhaps Gandalf — were to offer you a magical golden ring with the power to rid the world of mosquitoes once and for all. And with their demise, to save countless human lives from the many diseases for which mosquitoes are the sole or primary vectors: Malaria, dengue, West Nile virus, chikungunya, yellow fever, filariasis, tularemia, encephalitis, Zika fever, Keystone Virus, Rift Valley Fever…And not just mosquitoes. From within the folds of his cloak the wizard draws out an array of equally luminous rings with the power to cure genetic disorders like cystic fibrosis, hemophilia, and Down’s syndrome, to rid cities of mice and rats, and free the world’s farms of weeds and insect pests without the use of pesticides. Would you take them? Those rings exist and are now being refined and tested in the Elvin forges of academic, commercial, and government research facilities around the world. They go by various names, but collectively may be referred to as CRISPR-Cas Genome Editing Systems.
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.
A naturally occurring bacteria can stop the malaria parasite right in a mosquito’s gut
27573A. Bhattacharya, Quartz, 2023-08-04 07:55:34.
Scientists at a GlaxoSmithKline (GSK) research facility in Spain discovered that a strain of Delftia tsuruhatensis bacterium, named Tres Cantos 1 (TC1), inhibits the malaria parasite in mosquitoes, known as Plasmodium. Researchers suspected something was going on when the mosquitoes they were using to study malaria were resisting Plasmodium infections. As noted in the study published in the peer-reviewed journal Science yesterday (Aug. 3), TC1 secretes a molecule called harmane that attacks the Plasmodium parasite, which is transmitted to humans by the bite of a mosquito.When the researchers fed the existing strain to other malaria-spreading Anopholes mosquitoes—without any human tinkering like with the genetically-modified microbes—they found the bacteria “drastically reduces malaria parasite burden in the mosquito, potentially reducing transmission to humans significantly,” GSK said in an Aug. 3 press release.
Delftia tsuruhatensis TC1 symbiont suppresses malaria transmission by anopheline mosquitoes
27565W. Huang, J. Rodrigues, E. Bilgo, J. R. Tormo, J. D. Challenger, C. De Cozar-Gallardo, I. Pérez-Victoria, F. Reyes, P. Castañeda-Casado, E. J. Gnambani, D. F. d. S. Hien, M. Konkobo, B. Urones, I. Coppens, A. Mendoza-Losana, L. Ballell, A. Diabate, T. S., Science, 381:533-540. 2023-08-04 07:30:48.
Malaria control demands the development of a wide range of complementary strategies. We describe the properties of a naturally occurring, non?genetically modified symbiotic bacterium, Delftia tsuruhatensis TC1, which was isolated from mosquitoes incapable of sustaining the development of Plasmodium falciparum parasites. D. tsuruhatensis TC1 inhibits early stages of Plasmodium development and subsequent transmission by the Anopheles mosquito through secretion of a small-molecule inhibitor. We have identified this inhibitor to be the hydrophobic molecule harmane. We also found that, on mosquito contact, harmane penetrates the cuticle, inhibiting Plasmodium development. D. tsuruhatensis TC1 stably populates the mosquito gut, does not impose a fitness cost on the mosquito, and inhibits Plasmodium development for the mosquito?s life. Contained field studies in Burkina Faso and modeling showed that D. tsuruhatensis TC1 has the potential to complement mosquito-targeted malaria transmission control. Malaria mosquitoes can act as hosts to several microorganisms, including commensal bacterial species. Huang et al. noticed that some laboratory colonies of anopheline mosquitoes were incapable of transmitting malaria parasites. These insects also harbored a few cells of a bacterium called Delftia tsuruhatensis TC1, which produces a toxic alkaloid called harmane. Bacteria-produced harmane inhibited the development of female Plasmodium parasite gametes in the mosquito gut. Harmane was found to be a contact poison that could also cross the mosquito cuticle to kill developing malaria parasites. Contained field trials in Burkina Faso, coupled with modeling studies, showed that the bacterium has the potential to be deployed in mosquito breeding sites as a component of malaria control. ?Caroline Ash A naturally occurring bacterium of anopheline mosquitoes produces an alkaloid that arrests the development of co-occurring Plasmodium oocytes
Microbe stops mosquitoes from harboring malaria parasite
27567C. Offord, Science, 2023-08-03 07:31:08.
Researchers have tried to use microbes to control mosquito-borne diseases before. The virus-fighting bacterium Wolbachia pipientis has shown particular promise against dengue fever in recent clinical trials and is already used in some areas of the world. But most methods for blocking malaria-causing Plasmodium parasites, which are transmitted by different mosquito species from dengue, have relied on genetically modified bacteria. That’s a major obstacle to regulatory and public acceptance, Barillas-Mury notes, given the unknowns of releasing edited organisms into the wild. The latest news, commentary, and research, free to your inbox daily The bacterium in the new study, published today in Science, inhibits the malaria parasite without any genetic tinkering by humans. Janneth Rodrigues, a scientific lead in global health medicines R&D at GlaxoSmithKline, and colleagues stumbled across the microbe at a GSK research center in Spain, after noticing the mosquitoes they were using for malaria research were getting harder to infect with Plasmodium.
Cost-effectiveness of Precision Guided SIT for Control of Anopheles gambiae in the Upper River Region, The Gambia
27060G. William, R. Robyn, M. Agastya, M. S. C. Hector, S. Andrea, Z. David, G. I. Patrick, D. Umberto, Alessandro, M. M. John and A. Omar, bioRxiv, 2023.07.20.549762. 2023-07-22 06:41:45.
Precision-guided sterile insect technique (pgSIT) is an extremely promising vector control intervention that can reduce and potentially eliminate the unacceptable malaria burden, particularly in sub-Saharan Africa. Here we explore the cost effectiveness of using this approach in Africa using mathematical modeling and economical analysis. Overall, we find that pgSIT represents a cost-effective and promising approach to A. gambiae control in The Gambia, with the potential to deliver significant economic and social benefits.Competing Interest StatementThis work was supported by funding from an Open Philanthropy award (309937-0001). The views, opinions, and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the U.S. government. Figures were created using www.BioRender.com.
Eliminating Malaria Vectors with Precision Guided Sterile Males
27058L. S. Andrea, A. A. Reema, J. P. James, L. C. Martha, C. Sanle, M. Agastya, M. S. C. Hector, A. Igor, M. M. John and S. A. Omar, bioRxiv, 2023.07.20.549947. 2023-07-21 06:35:41.
Controlling the principal African malaria vector, the mosquito Anopheles gambiae, is considered essential to curtail malaria transmission. However existing vector control technologies rely on insecticides, which are becoming increasingly ineffective. Sterile insect technique (SIT) is a powerful suppression approach that has successfully eradicated a number of insect pests, yet the A. gambiae toolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass-releases of non-biting, non-driving, sterile males which seek out and mate with monandrous wild females. Once mated, females are permanently sterilized due to mating-induced refractoriness, which results in population suppression of the subsequent generation. However, sterilization by traditional methods renders males unfit, making the creation of precise genetic sterilization methods imperative. Here we develop precision guided Sterile Insect Technique (pgSIT) in the mosquito A. gambiae for inducible, programmed male-sterilization and female-elimination for wide scale use in SIT campaigns. Using a binary CRISPR strategy, we cross separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding >99.5% male-sterility and >99.9% female-lethality in hybrid progeny. We demonstrate that these genetically sterilized males have good longevity, are able to induce population suppression in cage trials, and are predicted to eliminate wild A. gambiae populations using mathematical models, making them ideal candidates for release. This work provides a valuable addition to the malaria genetic biocontrol toolkit, for the first time enabling scalable SIT-like confinable suppression in the species.Competing Interest StatementO.S.A is a founder of Agragene, Inc. and Synvect, Inc. 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 other authors declare no competing interests.
Bukedi sub-region to receive new high-level malaria prevention technology
26950Watchdog Uganda, WATCHDOG, 2023-07-20 08:51:14.
President Yoweri Kaguta Museveni together with a group of scientists have agreed to start with Bukedi Sub-region as a pilot area for a new mosquito radiation sterilisation technology aimed at preventing malaria. “Let us start with the Bukedi Sub- region to pilot this method since the area has got a lot of water, flat area, and stagnant water. This will help us solve the problem of mosquitoes and have less patients,” President Museveni noted. Speaking during a meeting at State House, Entebbe yesterday, the President said if the study works out in Bukedi, the technology will then be spread to other areas around the country. “Sterilisation of the male mosquitoes or tsetse flies is something we have been talking about for a long time. But now, you have come, good, I support it, go ahead and have like a pilot effort which will result into a study and conclusion,” he appealed.
Mosquitoes spread malaria. These researchers want them to fight it instead
26948G. Brumfiel, NPR, 2023-07-20 08:45:44.
Mosquitoes carry malaria, which kills hundreds of thousands of people each year. Now some researchers are trying to use genetic engineering to make the pesky insects into allies in the fight against the disease. The approach is a radical departure from traditional ways of controlling malaria. For years, public health officials have tried to limit the disease by controlling mosquito populations. But that approach is temporary, says Anthony James, a professor of molecular biology and genetics at the University of California, Irvine. Because mosquitoes are extremely tough little insects, and their populations can quickly rebound. "To try to get rid of them, I don't think it's possible," he says. Instead, James and his colleagues want to try a different approach: making mosquitoes themselves into malaria-fighting warriors.
Engineered Gut Symbiotic Bacterium-Mediated RNAi for Effective Control of Anopheles Mosquito Larvae
27559J. J. Ding, C. L. Cui, G. D. Wang, G. Wei, L. Bai, Y. F. Li, P. L. Sun, L. Dong, Z. C. Liu, J. Q. Yun, F. Li, K. Li, L. He and S. B. Wang, Microbiology Spectrum, 2023-07-17 06:46:02.
Anopheles mosquitoes are the primary vectors for the transmission of malaria parasites, which poses a devastating burden on global public health and welfare. The recent invasion of Anopheles stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. To address this issue, we developed a new approach for mosquito larvae control using gut microbiota-mediated RNA interference (RNAi). We engineered a mosquito symbiotic gut bacterium, Serratia fonticola, by deleting its RNase III gene to produce double-stranded RNAs (dsRNAs) in the mosquito larval gut. We found that the engineered S. fonticola strains can stably colonize mosquito larval guts and produce dsRNAs dsMet or dsEcR to activate RNAi and effectively suppress the expression of methoprene-tolerant gene Met and ecdysone receptor gene EcR, which encode receptors for juvenile hormone and ecdysone pathways in mosquitoes, respectively. Importantly, the engineered S. fonticola strains markedly inhibit the development of A. stephensi larvae and leads to a high mortality, providing an effective dsRNA delivery system for silencing genes in insects and a novel RNAi-mediated pest control strategy. Collectively, our symbiont-mediated RNAi (smRNAi) approach offers an innovative and sustainable method for controlling mosquito larvae and provides a promising strategy for combating malaria.IMPORTANCE Mosquitoes are vectors for various diseases, imposing a significant threat to public health globally. The recent invasion of A. stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. RNA interference (RNAi) is a promising approach that uses dsRNA to silence specific genes in pests. This study presents the use of a gut symbiotic bacterium, Serratia fonticola, as an efficient delivery system of dsRNA for RNAi-mediated pest control. The knockout of RNase III, a dsRNA-specific endonuclease gene, in S. fonticola using CRISPR-Cas9 led to efficient dsRNA production. Engineered strains of S. fonticola can colonize the mosquito larval gut and effectively suppress the expression of two critical genes, Met and EcR, which inhibit mosquito development and cause high mortality in mosquito larvae. This study highlights the potential of exploring the mosquito microbiota as a source of dsRNA for RNAi-based pest control. Mosquitoes are vectors for various diseases, imposing a significant threat to public health globally. The recent invasion of A. stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides.
CRISPR’d Mosquitoes With All-Male Offspring Could Help Eradicate Malaria
26610V. B. Ramirez, Singuarity Hub, 2023-07-13 13:17:26.
Though at least one vaccine for malaria is in use, it remains one of the deadliest diseases in the world. Almost half of the world’s population lives in areas where malaria transmission occurs, and an estimated 619,000 people died of the disease in 2021. Worse yet, the vast majority of cases leading to death are in young children. Researchers from the University of California in San Diego may have found a way to reduce this burden of disease. They used the gene editing tool CRISPR to alter a gene that controls sexual development in mosquitoes. Male mosquitoes don’t bite humans; it’s the females that spread malaria and other diseases. The UCSD team’s method uses gene editing to kill all female mosquito offspring within a given population of the insects. The mosquito species in question is Anopheles gambiae, commonly called the African malaria mosquito and described as “the most efficient vector of human malaria.” They’re anthropophilic, meaning they like human blood more than animal blood, and they thrive in hot climates with a lot of moisture. Why such an insect exists in the first place is hard to comprehend, is it not?
Dual effector population modification gene-drive strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii
26580R. Carballar-Lejarazú, Y. Dong, T. B. Pham, T. Tushar, R. M. Corder, A. Mondal, H. M. Sánchez C, H.-F. Lee, J. M. Marshall, G. Dimopoulos and A. A. James, Proceedings of the National Academy of Sciences, 120:e2221118120. 2023-07-11 05:52:31.
Proposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)?based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti-Plasmodium falciparum effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes Anopheles gambiae (AgTP13) and Anopheles coluzzii (AcTP13). The gene-drive systems achieved full introduction within 3 to 6 mo after release in small cage trials. Life-table analyses revealed no fitness loads affecting AcTP13 gene-drive dynamics but AgTP13 males were less competitive than wild types. The effector molecules reduced significantly both parasite prevalence and infection intensities. These data supported transmission modeling of conceptual field releases in an island setting that shows meaningful epidemiological impacts at different sporozoite threshold levels (2.5 to 10 k) for human infection by reducing malaria incidence in optimal simulations by 50 to 90% within as few as 1 to 2 mo after a series of releases, and by ≥90% within 3 mo. Modeling outcomes for low sporozoite thresholds are sensitive to gene-drive system fitness loads, gametocytemia infection intensities during parasite challenges, and the formation of potentially drive-resistant genome target sites, extending the predicted times to achieve reduced incidence. TP13-based strains could be effective for malaria control strategies following validation of sporozoite transmission threshold numbers and testing field-derived parasite strains. These or similar strains are viable candidates for future field trials in a malaria-endemic region.
Mosquitoes made immune to malaria could help stamp out the disease
26614C. Wilson, NewScientist, 2023-07-10 13:29:44.
Mosquitoes have been gene edited so they are immune to the parasites that cause malaria. If released into the wild, the genetic modification should spread through a population of mosquitoes because it contains a sequence known as a “gene drive”, which means all the modified insects’ offspring would inherit the immunity. This approach could slash the numbers of malaria cases in people. Malaria is one of the world’s leading causes of death and ill health, taking a particular toll on young children in sub-Saharan Africa. Two vaccines have recently been developed, but they only give partial immunity. Other high-tech strategies against mosquito-borne diseases are under investigation, including gene drives that kill all mosquitoes in a targeted area. But these could have unpredictable effects on ecosystems, says Anthony James at the University of California, Irvine.
Routes of Introduction of Anopheles gambiae Into Remote Islands in the Indian Ocean
26612R. E. Ditter, M. Campos, M. W. Crepeau, J. Pinto, A. Toilibou, Y. Amina, Y. Lee, A. J. Cornel and G. C. Lanzaro, 2023-07-07 13:23:28.
The malaria vector Anopheles gambiae s.s., is a primary malaria vector throughout sub-Saharan Africa including the islands of the Comoros archipelago (Anjouan, Grande Comore, Mayotte and Mohéli). These islands are located at the northern end of the Mozambique Channel in eastern Africa. Previous studies have shown a relatively high degree of genetic isolation between island and mainland populations of A. gambiae, but the origin of the island populations remains unclear. Here, we analyzed phylogenetic relationships among island and mainland populations using complete mitochondrial genome sequences of individual A. gambiae specimens. We investigated the source population of A. gambiaefor each island, determined the number of introductions and estimated when they occurred, and explored evidence for contemporary gene flow between island and mainland populations. Phylogenetic analysis and haplotype networks were constructed from mitogenome sequences of 258 A. gambiae from the four islands. In addition, 112 individuals from seven countries across sub-Saharan Africa and Madagascar were included to identify potential source populations. Our results suggest that introduction events of A. gambiae into the Comoros archipelago were rare and recent events and that there is no evidence of contemporary migration between the islands and mainland Africa. This study further supports the suitability of these oceanic islands as appropriate sites for conducting field trial releases of genetically engineered mosquitoes (GEMs).
New Genetic Technology Developed to Halt Malaria-Spreading Mosquitoes
26473M. Aguilera, UC San Diego Today, 2023-07-05 08:09:31.
Fortunately, scientists are developing safe technologies to stop the transmission of malaria by genetically editing mosquitoes that spread the parasite that causes the disease. Researchers at the University of California San Diego led by Professor Omar Akbari’s laboratory have engineered a new way to genetically suppress populations of Anopheles gambiae, the mosquitoes that primarily spread malaria in Africa and contribute to economic poverty in affected regions. The new system targets and kills females of the A. gambiae population since they bite and spread the disease. Publishing July 5 in the journal Science Advances, first-author Andrea Smidler, a postdoctoral scholar in the UC San Diego School of Biological Sciences, along with former master’s students and co-first authors James Pai and Reema Apte, created a system called Ifegenia, an acronym for “inherited female elimination by genetically encoded nucleases to interrupt alleles.” The technique leverages the CRISPR technology to disrupt a gene known as femaleless (fle) that controls sexual development in A. gambiae mosquitoes.
Malaria Cases In U.S. Trigger Unfounded Claims About Bill Gates, Mosquito Project
26378B. Y. Lee, Forbes, 2023-07-01 07:03:59.
When the U.S. Centers for Disease Control and Prevention (CDC) issued an alert about finding four malaria cases in Florida and one malaria case in Texas, it created quite a buzz. After all, these were the first reported cases of people actually catching malaria in the U.S. since 2003. Finding these five cases has raised questions about whether malaria may return to the U.S. after being largely absent for many years and whether climate change may be opening the gates for Anopheles mosquitoes to spread in the U.S. That would kind of suck since the females of certain Anopheles mosquito species can carry and transmit malaria-causing parasites. This news also opened the gates in another way—allowing a flood of even more conspiracy theories about billionaire philanthropist Bill Gates to be spread across social media. This included claims that Gates was somehow responsible for these new malaria cases via a project that has released genetically-modified mosquitoes in the U.S. However, such claims really provided zzzzzero supporting evidence and, in fact, detracted from what’s really happened.
Wolbachia -induced inhibition of O’nyong nyong virus in Anopheles mosquitoes is mediated by Toll signaling and modulated by cholesterol
26465S. Pujhari, G. L. Hughes, N. Pakpour, Y. Suzuki and J. L. Rasgon, bioRxiv, 10.1101/2023.05.31.543096. 2023-06-01 07:41:43.
Enhanced host immunity and competition for metabolic resources are two main competing hypotheses for the mechanism of Wolbachia -mediated pathogen inhibition in arthropods. Using an Anopheles mosquito - somatic Wolbachia infection - O'nyong nyong virus (ONNV) model, we demonstrate that the mechanism underpinning Wolbachia -mediated virus inhibition is up-regulation of the Toll innate immune pathway. However, the viral inhibitory properties of Wolbachia were abolished by cholesterol supplementation. This result was due to Wolbachia -dependent cholesterol-mediated suppression of Toll signaling rather than competition for cholesterol between Wolbachia and virus. The inhibitory effect of cholesterol was specific to Wolbachia -infected Anopheles mosquitoes and cells. These data indicate that both Wolbachia and cholesterol influence Toll immune signaling in Anopheles mosquitoes in a complex manner and provide a functional link between the host immunity and metabolic competition hypotheses for explaining Wolbachia -mediated pathogen interference in mosquitoes. In addition, these results provide a mechanistic understanding of the mode of action of Wolbachia -induced pathogen blocking in Anophelines, which is critical to evaluate the long-term efficacy of control strategies for malaria and Anopheles -transmitted arboviruses. HIGHLIGHTS: Wolbachia inhibits O'nyong nyong virus (ONNV) in Anopheles mosquitoes. Enhanced Toll signaling is responsible for Wolbachia -induced interference of ONNV. Cholesterol suppresses Toll signaling to modulate Wolbachia -induced ONNV interference.
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.
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
First transgenic mosquito made in Africa by Transmission Zero
24962H. Dunning, Imperial College London, 2023-04-04 10:33:04.
Transmission Zero, a global scientific programme led by scientists at Imperial College London and the Ifakara Health Institute (IHI) of Tanzania, in partnership with the Tanzanian National Institute of Medical Research (NIMR), announces the generation of the first transgenic mosquito strain ever to be made in Africa.This strain carries in its genome genetic modifications that will allow scientists in the future to render mosquitoes unable to transmit malaria. This major scientific achievement is a pivotal milestone in the renewed international efforts to rid Africa of malaria. Half of the world’s population is at risk of contracting malaria, a disease caused by parasites that are transmitted from one person to another through mosquito bites. In 2021 alone, there were over 247 million cases and 619,000 deaths from malaria, mostly children under five years old in sub-Saharan Africa.
Gene Drives Are Coming
24887D. Lowe, Science, 2023-03-23 08:26:31.
Consider the “gene drive” idea - there are a lot of variations, but the general idea is that you introduce a genetic sequence into an organism that can bias (drive) its own inheritance into the next generation. This is a thumb-on-the-scale unnatural selection if ever there was one, because that biased inheritance is outside of any fitness advantage that the new sequence might bring with it. In fact, a number of gene drive ideas have the opposite sign, conferring catastrophic unfitness in order to wipe out pathogens and disease-vector organisms.Gene drives of various kinds show up in nature, though, when a gene has some sort of ability to control its own transmission. These are the so-called “selfish genes”, and some of these have no fitness advantage (or even some disadvantage) in the organisms themselves. There are a lot of potential mechanisms for this (see that link for a good review), but what you don’t see are the total-wipeout forms just mentioned, which is what we has humans might like to do to (say) mosquitos or tsetse flies. The advent of CRISPR-Cas9 technology has really brought a lot more attention to these ideas, because they make them far more possible, for better or worse.
Gene Drives: Target Malaria is underestimating the risks
24867C. Then, Testbiotech, 2023-03-17 07:55:56.
The Target Malaria consortium has for several years been planning to conduct field trials using genetically engineered mosquitoes in Burkina Faso. The aim is to transfer artificial gene constructs, i. e. the so-called ‘X-shredder’, into wild populations of the mosquitoes. This gene construct is meant to reduce the number of female offspring, and thus bring about a decline in the overall population of mosquitoes (Anopheles gambiae) known to transmit malaria. However, as recent research shows, the planned releases are based on flawed data and incorrect assumptions.
Modeling Sustained Transmission of Wolbachia among Anopheles Mosquitoes: Implications for Malaria Control in Haiti
24916D. Florez, A. J. Young, K. J. Bernabé, J. M. Hyman and Z. Qu, Trop Med Infect Dis, 8. 2023-03-09 12:09:17.
Wolbachia infection in Anopheles albimanus mosquitoes can render mosquitoes less capable of spreading malaria. We developed and analyzed a mechanistic compartmental ordinary differential equation model to evaluate the effectiveness of Wolbachia-based vector control strategies among wild Anopheles mosquitoes in Haiti. The model tracks the mosquito life stages, including egg, larva, and adult (male and female). It also accounts for critical biological effects, such as the maternal transmission of Wolbachia through infected females and cytoplasmic incompatibility, which effectively sterilizes uninfected females when they mate with infected males. We derive and interpret dimensionless numbers, including the basic reproductive number and next-generation numbers. The proposed system presents a backward bifurcation, which indicates a threshold infection that needs to be exceeded to establish a stable Wolbachia infection. The sensitivity analysis ranks the relative importance of the epidemiological parameters at baseline. We simulate different intervention scenarios, including prerelease mitigation using larviciding and thermal fogging before the release, multiple releases of infected populations, and different release times of the year. Our simulations show that the most efficient approach to establishing Wolbachia is to release all the infected mosquitoes immediately after the prerelease mitigation process. Moreover, the model predicts that it is more efficient to release during the dry season than the wet season.
Gene Drives and Vector-Borne Diseases: A Comparative Perspective Using Malaria as a Case Study
24818S. Todi, The Takshashila Institution, 2023-03-07 15:51:15.
Gene drives are an emerging technological application to reduce the prevalence of vector-borne diseases, crop pests, and non-native invasive species. This method for vector control is currently at the research stage, with parallel community engagement programmes being carried out in African countries to raise awareness for its adoption. Yet, the risks associated with using gene drives may go beyond the communities they are deployed in. Hence, it is critical for India to understand the relevance of gene drive application in India and its neighboring countries to create effective policy measures for achieving control of vector-borne diseases. Using malaria as a case study, we argue that India currently does not require the use of gene drives to achieve control of mosquito-borne diseases. However, India should invest in research for gene drives and vaccines, while continuing with current efforts to curb vector-borne diseases. Further, India will need strong data monitoring systems to identify if any gene drive mosquitoes deployed by other countries make their way to India.
Hybrid incompatibilities in the anopheles gambiae species complex
24968A. Kriezis, Imperial College London, 2023-03-01 10:47:20.
Malaria is an infectious disease caused by parasites of the genus Plasmodium which is responsible for approximately 400,000 deaths annually, primarily in sub-Saharan Africa. Malaria is transmitted by mosquitoes belonging to the Anopheles gambiae species complex. While progress has been made to reduce the incidence of malaria, the emergence of insecticide resistance necessitates the development of novel vector control strategies. Gene drive technologies have seen significant advances in recent years, providing hope for their implementation in the near future. While gene flow has been identified between sibling species of the An. gambiae species complex, they are reproductively isolated by both pre- and post-zygotic isolation mechanisms. Interspecific crosses between most member species produce sterile hybrid males, in accordance with Haldane’s rule of speciation. The aim of this project was to support the development of gene drive technologies by investigating hybrid incompatibilities between two of the most significant vector species, Anopheles gambiae and Anopheles arabiensis. The potential for the introgression of genomic regions from one species into the genetic background of the other was investigated to help inform models regarding the spread of gene drives between sibling species. In addition, the identification of genetic elements involved in hybrid male sterility could provide potential targets for vector control strategies. Large autosomal regions were found to introgress and persist in interspecific genomes without a detectable fertility cost. In addition, the introduction of distinct autosomal regions of conspecific DNA into otherwise heterospecific genomes of hybrid males was found to overcome hybrid incompatibilities and partially restore fertility. While no specific genetic factors involved in hybrid incompatibilities could be identified, the results indicate that such factors are present at least on the X chromosome. Furthermore, the evidence suggests that asynapsis between interspecific homologous autosomes during gametogenesis plays a role in the manifestation of hybrid male sterility.
Gene Drives Could Fight Malaria and Other Global Killers but Might Have Unintended Consequences
24460M. Cobb, Scientific American, 2023-01-13 08:22:55.
Every year more than 600,000 people die from mosquito-transmitted malaria, most of them children under age five. Some insects that are disease vectors, such as mosquitoes, are currently expanding their range around the world, bringing new threats. Genetic engineering can fix this by permanently altering insect genes through what is known as a gene drive. This technology allows a chosen set of genes to alter an animal’s biology in some way, such as making them produce sterile offspring. The inability to reproduce then sweeps through a population, upending the laws of inheritance. The genes copy themselves exponentially from generation to generation, rapidly coming to dominate the whole population. Potentially, their careful use might save millions of lives by making mosquitoes unable to transmit malaria or by eliminating the insects entirely. The possibility of a definitive solution to major infectious diseases makes a compelling case for a such a techno fix.
Genetically modified mosquitoes … could CRISPR gene editing end malaria?
24315D. Wells, SelectScience, 2022-12-22 08:44:13.
Despite being a preventable and treatable disease, malaria is currently affecting the lives of more than 200 million people.1 This results in over half a million deaths per year, with 80% of this mortality occurring in children under the age of 5.2 In addition to the tragic social and humanitarian considerations, the economic losses to Africa attributed to malaria equate to around $12 billion a year.3 Hence, the public health burden of malaria is huge, and continued efforts in malaria control, elimination strategies, and case management are crucial to minimizing the devastation that malaria has on at-risk communities. In this article, we explore the innovative use of genetically modified mosquitoes as a means of fighting this devastating disease.
Determining the landscape of resistance to gene drives in the malaria mosquito
27631I. Morianou, Imperial College London, 2022-12-01 10:17:51.
Gene drives are engineered selfish genetic elements with the potential to spread throughout entire insect populations for sustainable vector control. Recently, a gene drive was shown to eliminate caged populations of the malaria mosquito by targeting the highly conserved female-specific exon of the doublesex gene. This caused females, homozygous for the gene drive, to develop as sterile intersex individuals, leading to the observed population crash. However, target site resistant alleles that block gene drive activity, whilst encoding a functional copy of the target gene, may halt gene drive spread in the wild. These may be naturally occurring or generated by the gene drive itself. This thesis presents a pipeline for the discovery, genetic engineering, and testing of putative drive-resistant variants. First, to investigate the potential for natural resistance, existing population genomics data were interrogated for the presence of natural single nucleotide polymorphisms (SNPs) at the highly conserved gene drive target region. To investigate the potential for drive-induced resistance, a high-throughput assay was designed to generate a high volume of mutations at the gene drive target site and screen them for their ability to restore dsx function. These methods yielded three putatively resistant SNPs: one natural polymorphism and two rare Cas9-induced mutations. These were engineered in the mosquito genome for testing, using a novel method termed CRISPR-mediated cassette exchange (CriMCE). It was confirmed that all three polymorphisms are functional and offer full, partial or no resistance to gene drive. Importantly, partial resistance to gene drive is being demonstrated for the first time. To mitigate observed resistance, gene drive systems targeting multiple sites simultaneously were developed. These showed improved drive dynamics and caused rapid elimination of caged mosquito populations within 7-8 generations. The experimental pipeline described here can be applied to pre-empt and mitigate resistance against any gene drive strategy, prior to field testing.
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.
Combining transgenesis with paratransgenesis to fight malaria
23802W. Huang, J. Vega-Rodriguez, C. Kizito, S.-J. Cha and M. Jacobs-Lorena, eLife, 11:e77584. 2022-10-25 06:30:55.
Malaria is among the deadliest infectious diseases, and Plasmodium, the causative agent, needs to complete a complex development cycle in its vector mosquito for transmission to occur. Two promising strategies to curb transmission are transgenesis, consisting of genetically engineering mosquitoes to express antimalarial effector molecules, and paratransgenesis, consisting of introducing into the mosquito commensal bacteria engineered to express antimalarial effector molecules. Although both approaches restrict parasite development in the mosquito, it is not known how their effectiveness compares. Here we provide an in-depth assessment of transgenesis and paratransgenesis and evaluate the combination of the two approaches. Using the Q-system to drive gene expression, we engineered mosquitoes to produce and secrete two effectors – scorpine and the MP2 peptide – into the mosquito gut and salivary glands. We also engineered Serratia, a commensal bacterium capable of spreading through mosquito populations to secrete effectors into the mosquito gut. Whereas both mosquito-based and bacteria-based approaches strongly reduced the oocyst and sporozoite intensity, a substantially stronger reduction of Plasmodium falciparum development was achieved when transgenesis and paratransgenesis were combined. Most importantly, transmission of Plasmodium berghei from infected to naïve mice was maximally inhibited by the combination of the two approaches. Combining these two strategies promises to become a powerful approach to combat malaria.
Target Malaria’s scientists are working to rid Africa of an ancient plague
23783D. Matthews, Vox, 2022-10-20 07:12:04.
This could very well be the last century in human history when people die from malaria. If and when we do eradicate the disease, the team at Target Malaria will probably deserve a big share of the credit. Their plan to use gene drive technology to wipe out species of mosquitoes carrying the parasitic illness represents the most promising path to eradicating a disease that killed on the order of 150 million to 300 million people over the 20th century, and still kills hundreds of thousands each year. Malaria used to be broadly common across most of the populated world, covering much of North America, Europe, Japan, and Australia, in addition to its current locations in Africa, Latin America, and South Asia. As the researchers Max Roser and Hannah Ritchie note, “poet Friedrich Schiller contracted the disease in Mannheim, Oliver Cromwell in Ireland, and Abraham Lincoln in Illinois.” Malaria no longer exists in those areas due to decades of public health measures like the drainage of mosquito breeding sites and use of pesticides like DDT, as well as economic development that gave residents resources to prevent and treat the disease.
Driving down malaria transmission with engineered gene drives
23780W. T. Garrood, P. Cuber, K. Willis, F. Bernardini, N. M. Page and R. E. Haghighat-Khah, Frontiers in Genetics, 13. 2022-10-19 07:08:43.
The last century has witnessed the introduction, establishment and expansion of mosquito-borne diseases into diverse new geographic ranges. Malaria is transmitted by female Anopheles mosquitoes. Despite making great strides over the past few decades in reducing the burden of malaria, transmission is now on the rise again, in part owing to the emergence of mosquito resistance to insecticides, antimalarial drug resistance and, more recently, the challenges of the COVID-19 pandemic, which resulted in the reduced implementation efficiency of various control programs. The utility of genetically engineered gene drive mosquitoes as tools to decrease the burden of malaria by controlling the disease-transmitting mosquitoes is being evaluated. To date, there has been remarkable progress in the development of CRISPR/Cas9-based homing endonuclease designs in malaria mosquitoes due to successful proof-of-principle and multigenerational experiments. In this review, we examine the lessons learnt from the development of current CRISPR/Cas9-based homing endonuclease gene drives, providing a framework for the development of gene drive systems for the targeted control of wild malaria-transmitting mosquito populations that overcome challenges such as with evolving drive-resistance. We also discuss the additional substantial works required to progress the development of gene drive systems from scientific discovery to further study and subsequent field application in endemic settings.
Introgression of a synthetic sex ratio distortion transgene into different genetic backgrounds of Anopheles coluzzii
23760P. Pollegioni, T. Persampieri, R. L. Minuz, A. Bucci, A. Trusso, S. Di Martino, C. Leo, M. Bruttini, M. Ciolfi, A. M. Waldvogel, F. Tripet, A. Simoni, A. Crisanti and R. Müller, Insect Molecular Biology, 2022-10-17 06:14:10.
The development of genetically modified mosquitoes (GMM) and their subsequent field release offers innovative approaches for vector control of malaria. A non-gene drive self-limiting male-bias Ag(PMB)1 strain has been developed in a 47-year-old laboratory G3 strain of Anopheles gambiae s.l. When Ag(PMB)1 males are crossed to wild-type females, expression of the endonuclease I-PpoI during spermatogenesis causes the meiotic cleavage of the X chromosome in sperm cells, leading to fertile offspring with a 95% male bias. However, WHO states that the functionality of the transgene could differ when inserted in different genetic backgrounds of An. coluzzii which is currently a predominant species in several West-African countries and thus a likely recipient for a potential release of self-limiting GMMs. In this study, we introgressed the transgene from the donor Ag(PMB)1 by six serial backcrosses into two recipient colonies of An. coluzzii that had been isolated in Mali and Burkina Faso. Scans of informative SNP markers and whole-genome sequencing analysis revealed a nearly complete introgression of chromosome 3 and X, but a remarkable genomic divergence in a large region of the chromosome 2 between the later backcrossed (BC6) transgenic offspring and the recipient paternal strains. These findings suggested to extend the backcrossing breeding strategy beyond BC6 generation and increase the introgression efficiency of critical regions that have ecological and epidemiological implications through the targeted selection of specific markers. Disregarding of differential introgression efficiency, we concluded that the phenotype of the sex ratio distorter is stabile in the BC6 introgressed An. coluzzii strains. This article is protected by copyright. All rights reserved.
Anopheles homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial structure
23734S. E. Champer, I. K. Kim, A. G. Clark, P. W. Messer and J. Champer, eLife, 11:e79121. 2022-10-14 06:37:55.
Recent experiments have produced several Anopheles gambiae homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such drives may be highly effective tools to combat malaria. One such homing drive, based on the zpg promoter driving CRISPR/Cas9, was able to eliminate a cage population of mosquitoes. A second version, purportedly improved upon the first by incorporating an X-shredder element (which biases inheritance towards male offspring), was similarly successful. Here, we analyze experimental data from each of these gene drives to extract their characteristics and performance parameters and compare these to previous interpretations of their experimental performance. We assess each suppression drive within an individual-based simulation framework that models mosquito population dynamics in continuous space. We find that the combined homing/X-shredder drive is actually less effective at population suppression within the context of our mosquito population model. In particular, the combined drive often fails to completely suppress the population, instead resulting in an unstable equilibrium between drive and wild-type alleles. By contrast, otherwise similar drives based on the nos promoter may prove to be more promising candidates for future development than originally thought.
Research: Scientists Modify Mosquitoes That Can’t Spread Malaria
23775N. Kharbanda, Onlymyhealth, 2022-10-07 07:00:18.
According to a research, scientists have found a way to genetically engineer mosquitoes with the capability to slow down the multiplication of malaria-causing parasites in their gut. This is an advance study, that can help in preventing the infecting of the disease in humans. The disease spreads in people because of a female mosquito when it bites someone infected with the malaria parasite. The parasite grows into the next stage in the mosquito’s gut and transports to its salivary glands, to infect the next human it bites. These modified mosquitoes produce compounds which interfere in the growth of malaria-causing parasites, which are then not able to reach the mosquitoes’ salivary glands and be passed on in a bite before the insects are dead. The team of researchers from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation have created a model which can analyse the effect of such changes if used in various African settings. They also found that the modification of these mosquitoes could be helpful even in locations where the transmission rate is high.
Explained: How Scientists Are Genetically modifying Mosquitoes To Reduce Malaria
23772Anonymous, Outlook, 2022-10-07 06:57:17.
he Delhi High Court on Friday asked the state government to inform it within two weeks of the proposal of increasing the fine amount in mosquito breeding cases. The court last year took suo moto cognizance of the issue of large-scale mosquito breeding in the city, resulting in the spread of vector-borne diseases With a sudden increase in malaria cases across the country, a recent research might provide some respite. Scientists have genetically modified mosquitoes to slow the growth of malaria-causing parasites in their guts — an advancement that can help prevent transmission of the disease to humans. Though only around 10 per cent of mosquitoes live long enough for the infectious parasite to develop, malaria remains one of the most devastating diseases globally, putting at risk about half of the world’s population. In 2021, it infected 241 million people and killed 627,000 people.
Malaria-free mosquito engineered by scientists
23697GNA, MODERN GHANA, 2022-10-03 07:54:35.
Scientists have genetically modified the main malaria-carrying species of mosquito in sub-SaharanAfrica to slow the growth of malaria-causing parasites in their gut, preventing transmission of thedisease to humans. When the Anopheles gambiae takes a blood meal, it produces two molecules called antimicrobialpeptides in its guts, according to the scientists. These peptides, which were originally isolated from honeybees and African clawed frogs, impair themalaria parasite's development. Now researchers from the Transmission Zero team at Imperial College London have come up with adesign that can be combined with existing “gene drive” technology to spread the modification anddrastically cut malaria transmission. Collaborators from the Institute for Disease Modelling at the Bill and Melinda Gates Foundation,which funded the research, also developed a model that, for the first time, can assess the impact ofsuch modifications if used in a variety of African settings. They found that the modification developed by the Imperial team could be a powerful tool forbringing down cases of malaria even where transmission is high.
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?
Scientists stunt parasite growth to tackle malaria
23769RSS24.news, RSS24.NEWS, 2022-09-29 06:52:01.
Loss of life, loss of livlihoods and homelessness have already afflicted these flood marooned refugees in Pakistan. Now these living conditions means they also face sickness and and without protection malaria is a major threat. Health agencies try to protect people against infection with sprays, nets and a vaccine for children, there are also preventative medicines. But despite all these, there were 241 million cases of malaria in 2020 and an estimated 627,000 deaths according to the latest malaria report from the World Health Organization (WHO). The WHO says these strategies, which are also used for other mosquito borne diseases such as Zika and dengue, are only partially effective. In the meantime the insects are becoming inceasingly resistant to insecticides. Scientists have for many years been investigating whether they can control the life cycle of mosquitoes by manipulating their DNA, thereby creating genetically modified mosquitoes. The disease is spread by a parasite Plasmodium falciparum which grows and reaches maturation inside the female Anopheles mosquito.
Scientists are manipulating the DNA of mosquitoes to fight the spread of malaria
23766R. Min, EURONEWS.NEXT, 2022-09-29 06:48:00.
Scientists say they have managed to genetically modify mosquitoes so that they are unable to spread malaria, a disease that kills well over half a million people each year. The changes cause mosquitoes to live shorter lives, while the parasites inside them, which cause the fatal infection, develop more slowly. This slashes the chances of mosquitoes living long enough to carry fully grown parasites – and transmit the disease to the humans they bite.Malaria is spread by the parasite Plasmodium falciparum, which grows and reaches maturation inside the female Anopheles mosquito. The average mosquito survives on average seven to 10 days in the wild. "By prolonging the developmental time that the parasite needs inside the mosquito to become infectious, this 10 per cent becomes now much smaller".
Scientists engineer mosquitoes that cannot spread malaria
23601J. Dalton, Independen, 2022-09-22 14:30:39.
Scientists have engineered mosquitoes that cannot give humans malaria, saying their work could potentially eliminate the disease. Researchers at Imperial College London genetically modified the insects so that the growth of malaria-causing parasites in their guts was slowed.
Scientists Engineer Mosquitoes That Can’t Transmit Malaria
23598C. Murez, US News, 2022-09-22 14:21:57.
The fight against malaria could hinge on genetically engineered mosquitoes that have something called "gene drive."Researchers from the Transmission: Zero team at Imperial College London report that they have engineered mosquitoes that slow the growth in their gut of the parasites that cause malaria. This delay would mean the mosquito would reach its natural life span before the parasite would reach the mosquitoes' salivary glands. So a bite wouldn't spread the disease. In the lab, this dramatically reduced the spread of malaria. "Since 2015, the progress in tackling malaria has stalled. Mosquitoes and the parasites they carry are becoming resistant to available interventions such as insecticides and treatments, and funding has plateaued. We need to develop innovative new tools," study co-author Tibebu Habtewold said in a college news release. He's a researcher from the college's Department of Life Sciences. Last year, malaria infected 241 million people, killing 627,000 of them, mostly children younger than age 5 in sub-Saharan Africa.
Mosquitoes that can’t spread malaria engineered by scientists
235842022-09-22 14:04:19.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes' salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria.The innovation, by researchers from the Transmission:Zero team at Imperial College London, is designed so it can be coupled with existing 'gene drive' technology to spread the modification and drastically cut malaria transmission. The team is looking towards field trials, but will thoroughly test the safety of the new modification before combining it with a gene drive for real-world tests. Collaborators from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation also developed a model that, for the first time, can assess the impact of such modifications if used in a variety of African settings. They found that the modification developed by the Transmission:Zero team could be a powerful tool for bringing down cases of malaria even where transmission is high.
Scientists engineer mosquitoes that can’t spread malaria
23581S. Varshney, Gamacher Central, 2022-09-22 13:58:18.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans. The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes’ salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria.
Mosquitoes with honeybee DNA could tame malaria
23579R. Blakely, The Times, 2022-09-22 13:53:23.
A new form of genetically engineered mosquito could reduce the spread of malaria in Africa, a study suggests. The addition of DNA from a honeybee and genetic material from the African clawed frog prompt the new mosquitoes to produce compounds to stunt the growth of the parasite that causes malaria. This means that the parasite, and therefore the disease, is less likely to be passed on to human victims via mosquito bite. To be useful in the real world this would have to be coupled with an existing technology known as a gene drive, a controversial genetic tool that would force the new characteristic through populations of mosquitoes as they reproduce. For malaria to spread, a female mosquito must bite someone infected with the malaria
Genetically Engineered Mosquitoes Prevented the Growth of Malaria-causing Parasites in Their Gut
23576P. Mozter, Nature World News 2022, 2022-09-22 13:45:51.
Abstract: Scientists have created mosquitoes that inhibit the development of malaria-causing parasites in their stomachs, therefore decreasing disease transmission to people. The genetic change allows mosquitoes to create substances in their intestines that inhibit parasite development, making parasites less likely to reach the mosquitoes' salivary glands and be transmitted in a bite before the insects die, as per ScienceDaily. The Transmission: Zero team at Imperial College London developed the breakthrough so that it may be used with current "gene drive" technologies to distribute the alteration and substantially reduce malaria transmission. The team is planning field experiments, but first, they will rigorously verify the new modification's safety before merging it with a gene drive for real-world testing.
Mosquitoes are being genetically modified so they can’t spread malaria
23596M. Le Page, New Scientist, 2022-09-21 14:17:06.
Gene editing mosquitoes so they die before malaria parasites can develop inside them could stop the spread of the deadly parasite entirely,
Genetically-modified mosquitoes could ‘help wipe out malaria’
23594S. Knapton, The Telegraph, 2022-09-21 14:11:56.
Mosquitoes that cannot spread malaria have been genetically engineered by British scientists, in a breakthrough that could help eliminate the disease. ...
Scientists engineer mosquitoes that can’t spread malaria
23572Imperial College London, Phys Org, 2022-09-21 13:32:19.
Scientists have engineered mosquitoes that slow the growth of malaria-causing parasites in their gut, preventing transmission of the disease to humans. The genetic modification causes mosquitoes to produce compounds in their guts that stunt the growth of parasites, meaning they are unlikely to reach the mosquitoes' salivary glands and be passed on in a bite before the insects die. So far, the technique has been shown to dramatically reduce the possibility of malaria spread in a lab setting, but if proven safe and effective in real-world settings it could offer a powerful new tool to help eliminate malaria. The innovation, by researchers from the Transmission:Zero team at Imperial College London, is designed so it can be coupled with existing "gene drive" technology to spread the modification and drastically cut malaria transmission. The team is looking towards field trials, but will thoroughly test the safety of the new modification before combining it with a gene drive for real-world tests. Collaborators from the Institute for Disease Modeling at the Bill and Melinda Gates Foundation also developed a model that, for the first time, can assess the impact of such modifications if used in a variety of African settings. They found that the modification developed by the Transmission:Zero team could be a powerful tool for bringing down cases of malaria even where transmission is high.
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.
A confinable female-lethal population suppression system in the malaria vector, Anopheles gambiae
23500A. L. Smidler, J. J. Pai, R. A. Apte, H. M. Sánchez C, R. M. Corder, E. J. Gutiérrez, N. Thakre, I. Antoshechkin, J. M. Marshall and O. S. Akbari, bioRxiv, 2022.08.30.505861. 2022-08-30 19:10:47.
Malaria is among the world’s deadliest diseases, predominantly affecting sub-Saharan Africa, and killing over half a million people annually. Controlling the principal vector, the mosquito Anopheles gambiae, as well as other anophelines, is among the most effective methods to control disease spread. Here we develop an innovative genetic population suppression system termed Ifegenia (Inherited Female Elimination by Genetically Encoded Nucleases to Interrupt Alleles) in this deadly vector. In this bicomponent CRISPR-based approach, we disrupt a female-essential gene, femaleless (fle), demonstrating complete genetic sexing via heritable daughter gynecide. Moreover, we show that Ifegenia males remain reproductively viable, and can load both fle mutations and CRISPR machinery to induce fle mutations in subsequent generations, resulting in sustained population suppression. Through modeling, we demonstrate that iterative releases of non-biting Ifegenia males can act as an effective, confinable, controllable, and safe population suppression and elimination system.
What do we mean by “Target Organism” in Target Malaria’s gene drive research?
23336J. B. Connolly, Target Malaria, 2022-07-27 08:46:32.
In the wild and in laboratory settings, sibling mosquito species can successfully mate to produce viable offspring, regardless of whether they are vectors or not. Importantly, females, but not males, of these offspring can be fertile. Nonetheless, the likelihood of finding such hybrid mosquitoes in field samples varies greatly between different combinations of species. According to some field studies, typically, only about 0.1% of mosquito collected in the wild could be An. gambiae s.s./An. coluzzii hybrids. In addition, some species that do not overlap geographically, and therefore would not come into direct contact, cannot produce hybrids in the field. This includes An. melas, which is found along the coast of West Africa, and An. bwambae, which is restricted to hot springs in the Toro District of Uganda. This means that the gene drive could eventually transfer to all sibling species of the complex, both by direct hybridisation between geographically-overlapping species and, indirectly, by transferring from one species to another overlapping ones like stepping-stones until the gene drive was transferred to all species of the complex, including to the likes of An. melas and An. bwambae
Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modelling study
23307S. Leung, N. Windbichler, E. A. Wenger, C. A. Bever and P. Selvaraj, Malaria Journal, 21:226. 2022-07-26 07:49:07.
BACKGROUND: Gene drives are a genetic engineering method where a suite of genes is inherited at higher than Mendelian rates and has been proposed as a promising new vector control strategy to reinvigorate the fight against malaria in sub-Saharan Africa. METHODS: Using an agent-based model of malaria transmission with vector genetics, the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission are examined and the population replacement gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting are quantified. The performance of two different gene drive systems-"classic" and "integral"-are evaluated. Various transmission regimes (low, moderate, and high-corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare-seeking, are also simulated. RESULTS: Local elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above ~ 80-90%). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as ~ 50% and in high transmission regimes with transmission-blocking effectiveness values above ~ 80-90%. CONCLUSION: A single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.
Lack of robust evidence for a Wolbachia infection in Anopheles gambiae from Burkina Faso
23300S. P. Sawadogo, D. A. Kabore, E. B. Tibiri, A. Hughes, O. Gnankine, S. Quek, A. Diabaté, H. Ranson, G. L. Hughes and R. K. Dabiré, Medical and Veterinary Entomology, 2022-07-25 07:31:44.
The endosymbiont Wolbachia can have major effects on the reproductive fitness, and vectorial capacity of host insects and may provide new avenues to control mosquito-borne pathogens. Anopheles gambiae s.l is the major vector of malaria in Africa but the use of Wolbachia in this species has been limited by challenges in establishing stable transinfected lines and uncertainty around native infections. High frequencies of infection of Wolbachia have been previously reported in An. gambiae collected from the Valle du Kou region of Burkina Faso in 2011 and 2014. Here, we re-evaluated the occurrence of Wolbachia in natural samples, collected from Valle du Kou over a 12-year time span, and in addition, expanded sampling to other sites in Burkina Faso. Our results showed that, in contrast to earlier reports, Wolbachia is present at an extremely low prevalence in natural population of An. gambiae. From 5341 samples analysed, only 29 were positive for Wolbachia by nested PCR representing 0.54% of prevalence. No positive samples were found with regular PCR. Phylogenetic analysis of 16S rRNA gene amplicons clustered across supergroup B, with some having similarity to sequences previously found in Anopheles from Burkina Faso. However, we cannot discount the possibility that the amplicon positive samples we detected were due to environmental contamination or were false positives. Regardless, the lack of a prominent native infection in An. gambiae s.l. is encouraging for applications utilizing Wolbachia transinfected mosquitoes for malaria control.
Comprehensive characterization of a transgene insertion in a highly repetitive, centromeric region of Anopheles mosquitoes
23273M. Vitale, C. Leo, T. Courty, N. Kranjc, J. B. Connolly, G. Morselli, C. Bamikole, R. E. Haghighat-Khah, F. Bernardini and S. Fuchs, Pathogens and Global Health, 2022-07-21 07:55:48.
The availability of the genomic sequence of the malaria mosquito Anopheles gambiae has in recent years sparked the development of transgenic technologies with the potential to be used as novel vector control tools. These technologies rely on genome editing that confer traits able to affect vectorial capacity. This can be achieved by either reducing the mosquito population or by making mosquitoes refractory to the parasite infection. For any genetically modified organism that is regarded for release, molecular characterization of the transgene and flanking sites are essential for their safety assessment and post-release monitoring. Despite great advancements, Whole-Genome Sequencing data are still subject to limitations due to the presence of repetitive and unannotated DNA sequences. Faced with this challenge, we describe a number of techniques that were used to identify the genomic location of a transgene in the male bias mosquito strain Ag(PMB)1 considered for potential field application. While the initial inverse PCR identified the most likely insertion site on Chromosome 3 R 36D, reassessment of the data showed a high repetitiveness in those sequences and multiple genomic locations as potential insertion sites of the transgene. Here we used a combination of DNA sequencing analysis and in-situ hybridization to clearly identify the integration of the transgene in a poorly annotated centromeric region of Chromosome 2 R 19D. This study emphasizes the need for accuracy in sequencing data for the genome of organisms of medical importance such as Anopheles mosquitoes and other tools available that can support genomic locations of transgenes.
Novel gene drive based on eliciting piRNA biogenesis in insect pests
23235C. Henderson and B. Christina, Rutgers Research, 2022-07-14 06:56:49.
Rutgers researchers have developed a potential permanent solution to persistent pest control issues by developing a system for genetic modification which could reduce the transmission of vector borne diseases (like malaria) from their insect vectors, or to establish expression of a desirable trait such as Bacillus thuringiensis susceptibility in crop pests. The inventors have demonstrated their solution through a transgenic construct that expresses an anti-malaria peptide in Anopheles gambiae alongside piRNAs which are designed to direct silencing towards a host gene required for reproduction. If the host silences the genetic construct, this silencing will be directed towards the host gene resulting in infertility. This platform can be used to create a gene drive that can prevent resistance formation and allow for rapid spread of a trait within a population
A population modification gene drive targeting both Saglin and Lipophorin disables Plasmodium transmission in Anopheles mosquitoes
23150E. I. Green, E. Jaouen, D. Klug, R. P. Olmo, A. Gautier, S. A. Blandin and E. Marois, bioRxiv, 2022.07.08.499187. 2022-07-08 09:32:53.
Lipophorin is an essential, highly expressed lipid transporter protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles gambiae Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite Plasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmit Plasmodium berghei expressing the P. falciparum circumsporozoite protein. To force the spread of this anti-malarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic gene Saglin and also cleaves wild type Lipophorin, causing the anti-malarial modified Lipophorin version to hitch-hike together with the Saglin drive. Although producing drive-resistant alleles, the Saglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarial Lipophorin::Sc2A10 allele. This combination is expected to affect parasite transmission by two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.Competing Interest StatementThe authors have declared no competing interest.
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.
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.
Testing non-autonomous antimalarial gene drive effectors using self-eliminating drivers in the African mosquito vector Anopheles gambiae
22689D. A. Ellis, G. Avraam, A. Hoermann, C. A. S. Wyer, Y. X. Ong, G. K. Christophides and N. Windbichler, PLOS Genetics, 18:e1010244. 2022-06-02 14:26:57.
Author summary Gene drive is a method that allows the genetic modification of entire populations of harmful organisms. Their application to tackle invasive species, agricultural pests or insect disease vectors has been suggested. For example, they could reduce the capacity of malaria mosquitoes to transmit this deadly disease to humans by producing effector molecules inhibiting the development of the Plasmodium parasite in the mosquito vector. We describe a strategy to modularize and test multiple transgenes destined for release, and to introduce only the minimal set of modifications needed into a mosquito population. We show how some elements, once no longer needed, can be made to self-eliminate from populations and we also study how several independent gene drive traits, located in different parts of the genome, can interact and propagate at the level of mosquito cage populations.
Modifying mosquitoes to suppress disease transmission: Is the long wait over?
22854J. R. Powell, Genetics, 2022-06-02 08:31:17.
For more than 50 years it has been a dream of medical entomologists and public health workers to control diseases like malaria and dengue fever by modifying, through genetics and other methods, the arthropods that transmit them to humans. A brief synopsis of the history of these efforts as applied to mosquitoes is presented; none proved to be effective in reducing disease prevalence. Only in the last few years have novel approaches been developed or proposed that indicate the long wait may be over. Three recent developments are particularly promising: CRISPR-Cas9 driven genetic modification, shifting naturally occurring allele frequencies, and microbe-based modifications. The last is the furthest along in implementation. Dengue fever incidence has been reduced between 40% and 96% in 4 different regions of the world where Wolbachia-infected Aedes aegypti have been established in the field. It is not yet clear how sustainable such control programs will prove to be, but there is good reason for optimism. In light of this, the time is ripe for reinvigorated research on vectors, especially genetics. Vector-borne diseases primarily affect under-developed countries and thus have not received the attention they deserve from wealthier countries with well-developed and funded biomedical research establishments.
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.
CRISPR/Cas9 mediates efficient site-specific mutagenesis of the odorant receptor co-receptor (Orco) in the malaria vector Anopheles sinensis
22554Y. Wang, X. F. He, L. Qiao, Z. R. Yu, B. Chen and Z. B. He, Pest Management Science, 11. 2022-04-28 14:52:27.
BACKGROUND Anopheles sinensis is the most widely distributed mosquito species and is the main transmitter of Plasmodium vivax malaria in China. Most previous research has focused on the mechanistic understanding of biological processes in An. sinensis and novel ways of interrupting malaria transmission. However, the development of functional genomics and genetics-based vector control strategies against An. sinensis remain limited because of insufficient site-specific genome editing tools. RESULTS We report the first successful application of the CRISPR/Cas9 mediated knock-in for highly efficient, site-specific mutagenesis in An. sinensis. The EGFP marker gene driven by the 3 x P3 promoter was precisely integrated into the odorant receptor co-receptor (Orco) by direct injections of Cas9 protein, double-stranded DNA donor, and Orco-gRNA. We achieved a mutation rate of 3.77%, similar to rates in other mosquito species. Precise knock-in at the intended locus was confirmed by polymerase chain reaction (PCR) amplification and sequencing. The Orco mutation severely impaired mosquito sensitivity to some odors and their ability to locate and discriminate a human host. CONCLUSION Orco was confirmed as a key mediator of multiple olfactory-driven behaviors in the An. sinensis life cycle, highlighting the importance of Orco as a key molecular target for malaria control. The results also demonstrated that CRISPR/Cas9 was a simple and highly efficient genome editing technique for An. sinensis and could be used to develop genetic control tools for this vector. (c) 2022 Society of Chemical Industry.
Genetically altered mosquitoes to close gaps in malaria fight
22248M. Murigi, People Daily, 2022-04-25 09:00:48.
In 2020, nearly 6.9 million cases of malaria and about 742 deaths were confirmed in Kenya according to the Kenya Malaria Indicator Survey (KMIS) 2020. Although the number of reported infections declined from 10.9 million in 2018, the disease is still one of the main health issues in the country despite being a largely preventable and treatable disease. Kenya is not the only country suffering from the burden of this life-threatening disease. According to World Health Organisation (WHO) latest world malaria report, there were an estimated 241 million malaria cases and 627,000 malaria deaths worldwide in 2020. This represents about 14 million more cases in 2020 compared to 2019, and 69,000 more deaths. The high number of malaria cases continues to be registered even though several efforts have been put in place towards malaria eradication. It is for this reason scientists and researchers are assessing the use of new tools to edit the genes of malaria-transmitting mosquitoes as they try to come up with a long-lasting solution towards control and elimination of this disease. “The war against malaria has been ongoing for decades. It has led to the development of several interventions strategies, such as antimalarial drugs, insecticide-treated nets, and vaccines among others. However, despite all the interventions, the disease has not been eradicated because there are increased cases of insecticide resistance in mosquitoes, which pose a significant public health concern,” says Dr Willy Kiprotich Tonui, EBS, the Chairman and Executive Director at the Environmental Health Safety (EHS) Consultancy Limited who also doubles up as the Founder and Head of Secretariat to African Genetic Biocontrol Consortium.
Wolbachia endosymbionts in two Anopheles species indicates independent acquisitions and lack of prophage elements
21788S. Quek, L. Cerdeira, C. L. Jeffries, S. Tomlinson, T. Walker, G. L. Hughes and E. Heinz, Microbial Genomics, 8. 2022-04-21 06:52:58.
Wolbachia is a genus of obligate bacterial endosymbionts that infect a diverse range of arthropod species as well as filarial nematodes, with its single described species, Wolbachia pipientis, divided into several ‘supergroups’ based on multilocus sequence typing. Wolbachia strains in mosquitoes have been shown to inhibit the transmission of human pathogens, including Plasmodium malaria parasites and arboviruses. Despite their large host range, Wolbachia strains within the major malaria vectors of the Anopheles gambiae and Anopheles funestus complexes appear at low density, established solely on PCR-based methods. Questions have been raised as to whether this represents a true endosymbiotic relationship. However, recent definitive evidence for two distinct, high-density strains of supergroup B Wolbachia within Anopheles demeilloni and Anopheles moucheti has opened exciting possibilities to explore naturally occurring Wolbachia endosymbionts in Anopheles for biocontrol strategies to block Plasmodium transmission. Here, we utilize genomic analyses to demonstrate that both Wolbachia strains have retained all key metabolic and transport pathways despite their smaller genome size, with this reduction potentially attributable to degenerated prophage regions. Even with this reduction, we confirmed the presence of cytoplasmic incompatibility (CI) factor genes within both strains, with wAnD maintaining intact copies of these genes while the cifB gene was interrupted in wAnM, so functional analysis is required to determine whether wAnM can induce CI. Additionally, phy logenetic analysis indicates that these Wolbachia strains may have been introduced into these two Anopheles species via horizontal transmission events, rather than by ancestral acquisition and subsequent loss events in the Anopheles gambiae species complex. These are the first Wolbachia genomes, to our knowledge, that enable us to study the relationship between natural strain Plasmodium malaria parasites and their anopheline hosts.
New frontiers in vector control
21717WHO, World Health Organization, 2022-04-11 09:17:11.
Ever since Sir Ronald Ross discovered malaria parasites in an Anopheles mosquito in 1897, controlling insect vectors has played an increasingly important role in reducing the burden of the disease. For decades after World War II, indoor residual spraying (IRS) with insecticides was the only weapon against mosquitoes and proved a blunt and reasonably effective instrument for protecting people inside their homes. Then, beginning in the early 2000s, insecticide-treated nets (ITNs) became a new addition to countries’ vector control strategies. Thanks, in part, to the wide deployment of these 2 WHO-recommended interventions, the world made remarkable gains against malaria in the period 2000–2015. But progress plateaued, and this troubling slowdown was exacerbated by COVID-19. According to WHO’s latest World malaria report, 2020 saw a rise in the global burden of malaria, with an estimated 627 000 deaths and 241 million new cases of the disease. Getting back on track, and meeting WHO’s targets of a 90% reduction in malaria case incidence and mortality rates by 2030, will require renewed global attention, increased funding, and continued research and development of new interventions, among other actions. In the field vector control, researchers are working on several innovations that aim to enhance efforts to combat the disease.
Cas9-mediated maternal-effect and derived resistance alleles in a gene-drive strain of the African malaria vector mosquito, Anopheles gambiae
21663R. Carballar-Lejarazú, T. Tushar, T. B. Pham and A. A. James, Genetics, 2022-04-07 15:16:08.
CRISPR/Cas9 technologies are important tools for the development of gene-drive systems to modify mosquito vector populations to control the transmission of pathogens that cause diseases such as malaria. However, one of the challenges for current Cas9-based drive systems is their ability to produce drive-resistant alleles resulting from insertions and deletions (indels) caused principally by nonhomologous end-joining following chromosome cleavage. Rapid increases in the frequency of such alleles may impair gene-drive dynamics. We explored the generation of indels in the germline and somatic cells in female gene-drive lineages using a series of selective crosses between a gene-drive line, AgNosCd-1, and wild-type mosquitoes. We find that potential drive-resistant mutant alleles are generated largely during embryonic development, most likely caused by deposition of the Cas9 endonuclease and guide RNAs in oocytes and resulting embryos by homozygous and hemizygous gene-drive mothers.
Expanding the flexibility of genome editing approaches for population control of the malaria mosquito
22226N. Kranjc, Imperial College London-PhD, 2022-04-01 15:50:55.
Discovery and adaptation of CRISPR-Cas systems for genome editing have allowed us to gain an efficient and yet simple tool for genetic manipulation in various fields of molecular biology and biotechnology. One of the most promising applications is the use of CRISPR-Cas9 endonuclease for gene drive systems as a population control strategy for various insect pests of medical and agricultural importance. Use of CRISPR-Cas9 endonuclease in gene drive applications has shown great promise in the laboratory, particularly for the control of Anopheles gambiae, the major vector of malaria. However, the performance of such gene drives can be limited by the range of available target sequences and by a propensity of existing endonuclease formulations to generate resistant mutations that hinder the gene drive’s efficiency. To expand the flexibility of gene drive systems, computational analysis was performed to identify additional Cas9 orthologs and their specificities that could usefully augment the targeting range of endonuclease-based gene drives. Two alternative variants of CRISPR-Cas endonucleases found in the bacterial species Lactobacillus rhamnosus and Bacteroides fragilis were assessed for their potential to expand the targeting space in the genome Anopheles gambiae. In addition, a computational tool was developed that evaluates neighbouring sequences to the target site to measure both its likely functional constraint and its likely propensity for DNA repair that could generate in-frame alleles. Using this approach we were able to generate a prioritized list of Anopheles gambiae target sites for gene drive applications that are less likely to be compromised by resistant alleles.
Mathematical modelling to assess the feasibility of Wolbachia in malaria vector biocontrol
22650S. Andreychuk and L. Yakob, Journal of Theoretical Biology, 542. 2022-03-29 06:30:06.
Releasing mosquitoes transinfected with the endosymbiotic bacterium Wolbachia is a novel strategy for interrupting vector-borne pathogen transmission. Following its success in controlling arboviruses spread by Aedes aegypti, this technology is being adapted for anopheline malaria vectors. However, antagonistic interactions between Wolbachia and naturally resident Asaia bacteria in malaria vectors have been demonstrated experimentally, potentially jeopardising Wolbachia biocontrol. We developed the first mathematical model accounting for interspecific competition between endosymbionts to assess the feasibility of this novel strategy for controlling malaria. First, Asaia prevalences among natural mosquito populations were compared with simulations parametrized with rates of Asaia transmission reported from laboratory studies. Discrepancies between projections and natural Asaia prevalences indicated potential overestimation of Asaia transmissibility in artificial laboratory settings. With parametrization that matches natural Asaia prevalence, simulations identified redundancies in Asaia's many infection routes (vertical, sexual and environmental). This resilience was only overcome when Wolbachia conferred very high resistance to environmental infection with Asaia, resulting in Wolbachia fixation and Asaia exclusion. Wolbachia's simulated spread was prevented when its maternal transmission was impeded in coinfected mosquitoes and the pre-control Asaia prevalence was beyond a threshold of 60-75%. This theoretical assessment highlights critical next steps in laboratory experiments to inform this strategy's feasibility. (c) 2022 The Author(s). Published by Elsevier Ltd.
Finding the strongest gene drive: Simulations reveal unexpected performance differences between Anopheles homing suppression drive candidates
21566S. E. Champer, I. K. Kim, A. G. Clark, P. W. Messer and J. Champer, bioRxiv, 2022.03.28.486009. 2022-03-28 12:29:28.
Recent experiments have produced several Anopheles gambiae homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such drives may be highly effective tools to combat malaria. One such homing drive, based on the zpg promoter driving CRISPR/Cas9, was able to eliminate a cage population of mosquitoes. A second version, purportedly improved upon the first by incorporating an X-shredder element (which biases inheritance towards male offspring), was similarly successful. Here, we re-analyze the data of each of these gene drives and suggest an alternative interpretation of their performance. We assess each suppression drive within an individual-based simulation framework that models mosquito population dynamics in continuous space. We find that the combined homing/X-shredder drive is actually less effective at population suppression within the context of our mosquito population model. In particular, the combined drive often fails to completely suppress the population, instead resulting in an unstable equilibrium between drive and wild-type alleles. By contrast, otherwise similar drives based on the nos promoter may prove to be more promising candidates for future development due to potentially superior performance.Competing Interest StatementThe authors have declared no competing interest.
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.
An Ethical Overview of the CRISPR-Based Elimination of Anopheles gambiae to Combat Malaria
20442I. J. Wise and P. Borry, Journal of Bioethical Inquiry, 2022-02-17 09:30:10.
Approximately a quarter of a billion people around the world suffer from malaria each year. Most cases are located in sub-Saharan Africa where Anopheles gambiae mosquitoes are the principal vectors of this public health problem. With the use of CRISPR-based gene drives, the population of mosquitoes can be modified, eventually causing their extinction. First, we discuss the moral status of the organism and argue that using genetically modified mosquitoes to combat malaria should not be abandoned based on some moral value of A. gambiae. Secondly, we argue that environmental impact studies should be performed to obtain an accurate account of the possible effects of a potential eradication of the organism. However, the risks from the purposeful extinction of A. gambiae should not overtake the benefits of eradicating malaria and risk assessments should be used to determine acceptable risks. Thirdly, we argue that the eventual release of the genetically modified mosquitoes will depend on transparency, community involvement, and cooperation between different nations.
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.
Gene-drive mosquitoes, a prospect for future malaria control
21770S. A. Monawwer, A. O. I. Alzubaidi, F. Yasmin, S. M. Q. Haimour, S. M. I. Shay and I. Ullah, Pan African Medical Journal, 41:2-6. 2022-02-08 07:58:25.
Despite major developments in malaria control over the past two decades, the disease continues to scourge the human population across the globe. Rising concerns such as insecticide resistance amongst vector mosquitoes are a cause of huge fear amongst healthcare providers and policymakers. Amidst such dire circumstances, a recent development may form the blueprint for future malaria control as for the first time ever researchers were able to decimate an entire mosquito population using gene-drive technology within a span of one year in a multi-generation, ecologically challenging study. Despite some concerns, the technology displayed a high potential of becoming a powerful tool in malaria control.
Scientists find transmission chain-breaker, give new hope for fight against malaria
20473ANI, ANI, 2022-01-27 08:09:19.
A recent study, published online in 'PLoS Biology', has revealed that blocking a key protein found in Anopheles gambiae mosquitoes -- the principal vector for malaria transmission to humans in Africa could thwart infection with malaria parasites and thus prevent them from transmitting the parasites to humans. The study was undertaken by Johns Hopkins Malaria Research Institute at the Johns Hopkins Bloomberg School of Public Health. In a lab experiment, the researchers used CRISPR/Cas9 gene-editing technology to delete the gene for a protein called CTL4 from Anopheles gambiae mosquitoes. This deletion made the mosquitoes highly resistant to the malaria parasite. The researchers found that disrupting the CTL4 protein brought a 64 percent decrease in infection prevalence. The researchers believe that targeting the CTL4 protein could be the basis for new strategies to control malaria in regions where it is still endemic.
Beyond the eye: Kynurenine pathway impairment causes midgut homeostasis dysfunction and survival and reproductive costs in blood-feeding mosquitoes
19915V. Bottino-Rojas, I. Ferreira, R. D. Nunes, X. Feng, T. B. Pham, A. Kelsey, R. Carballar-Lejarazú, V. Gantz, P. L. Oliveira and A. A. James, Insect Biochemistry and Molecular Biology, 103720. 2022-01-06 08:57:05.
Insect ommochrome biosynthesis pathways metabolize tryptophan to generate eye-color pigments and naturally occurring alleles of pathway genes are useful phenotypic markers in transgenesis studies. Pleiotropic effects of mutations in some genes exert a load on both survival and reproductive success in blood-feeding species. Here, we investigated the challenges imposed on mosquitoes by the increase of tryptophan resulting from blood meal digestion and the impact of disruptions of the ommochrome biosynthesis pathway. Female mosquitoes with spontaneous and induced mutations in the orthologs of the genes encoding kynurenine hydroxylase in Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus exhibited impaired survival and reproductive phenotypes that varied in type and severity among the species. A compromised midgut permeability barrier function was also observed in An. stephensi. Surprisingly, mutant mosquitoes displayed an increase in microbiota compared to controls that was not accompanied by a general induction of immune genes. Antibiotic treatment rescued some deleterious traits implicating a role for the kynurenine pathway (KP) in midgut homeostasis. Supplemental xanthurenic acid, a KP end-product, rescued lethality and limited microbiota proliferation in Ae. aegypti. These data implicate the KP in the regulation of the host/microbiota interface. These pleiotropic effects on mosquito physiology are important in the development of genetic strategies targeting vector mosquitoes.
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.
Three Decades of Malaria Vector Control in Sudan: The Plausible Role of Sterile Insect Technique (SIT)
19977A. Elaagip and A. Adedapo, Genetically Modified and other Innovative Vector Control Technologies, 2021-12-21 11:51:34.
In Northern State, Sudan, a feasibility study for sterile insect technique (SIT) in an area-wide integrated pest management was established for the first time in an African country. The aim of the study was to see whether it is feasible, from a technical, an economical and a biological perspective, to use sterile male mosquitoes to control mosquito populations in designated areas in the African context. The project was focussed on Anopheles arabiensis, one of the major malaria vectors. Meteorological data, larval surveillance and population genetic studies were carried out on the disease vectors. The first phase of the study focussed on the development of an efficient sex-separation system, development of dose-sterility curves for the pupal and adult stages and testing of a range of doses in competition experiments to determine effective sterility dose. This stage was followed by a semi-field phase that monitored their swarming and mating behaviours, effectiveness of irradiated males in competitive experiments with wild males and insemination rates. Information regarding irradiation and transportation of irradiated males were also obtained during the study. Unfortunately, the SIT study was terminated in 2017 before starting field release of irradiated males. In spite of the challenges, such investment need not be totally abandoned as valuable experience has been gained and capacity built, which are of high value to malaria control program in Sudan.
Modeling impact and cost-effectiveness of driving-Y gene drives for malaria elimination in the Democratic Republic of the Congo
19594N. Metchanun, C. Borgemeister, G. Amzati, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin, Evolutionary Applications, 2021-12-07 17:59:09.
Malaria elimination will be challenging in countries that currently continue to bear high malaria burden. Sex-ratio distorting gene drives, such as driving-Y, could play a role in an integrated elimination strategy if they can effectively suppress vector populations. Using a spatially explicit, agent-based model of malaria transmission in eight provinces spanning the range of transmission intensities across the Democratic Republic of the Congo, we predict the impact and cost-effectiveness of integrating driving-Y gene drive mosquitoes in malaria elimination strategies that include existing interventions such as insecticide-treated nets and case management of symptomatic malaria. Gene drive mosquitoes could eliminate malaria and were the most cost-effective intervention overall if the drive component was highly effective with at least 95% X-shredder efficiency at relatively low fertility cost, and associated cost of deployment below 7.17 $int per person per year. Suppression gene drive could be a cost-effective supplemental intervention for malaria elimination, but tight constraints on drive effectiveness and cost ceilings may limit its feasibility.
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-resolution in situ analysis of Cas9 germline transcript distributions in gene-drive Anopheles mosquitoes
19324G. Terradas, A. Hermann, A. A. James, W. McGinnis and E. Bier, G3-Genes Genomes Genetics, 2021-11-15 14:20:36.
Gene drives are programmable genetic elements that can spread beneficial traits into wild populations to aid in vector-borne pathogen control. Two different drives have been developed for population modification of mosquito vectors. The Reckh drive (vasa-Cas9) in Anopheles stephensi displays efficient allelic conversion through males but generates frequent drive-resistant mutant alleles when passed through females. In contrast, the AgNosCd-1 drive (nos-Cas9) in Anopheles gambiae achieves almost complete allelic conversion through both genders. Here, we examined the subcellular localization of RNA transcripts in the mosquito germline. In both transgenic lines, Cas9 is strictly coexpressed with endogenous genes in stem and premeiotic cells of the testes, where both drives display highly efficient conversion. However, we observed distinct colocalization patterns for the two drives in female reproductive tissues. These studies suggest potential determinants underlying efficient drive through the female germline. We also evaluated expression patterns of alternative germline genes for future gene-drive designs.
Two years of laboratory studies on the non gene drive genetically modified sterile male mosquitoes concluded successfully in Mali
19224M. Coulibaly, Target Malaria, 2021-11-09 21:44:38.
The Target Malaria Mali team at the Malaria Research and Training Centre (MRTC) based at the University of Sciences, Techniques and Technologies of Bamako (USTTB) is proud to have been the first Malian research team to work on non gene drive genetically modified sterile male mosquitoes. The team has just published the results of the two years we spent studying these mosquitoes in our laboratory. Thanks to this research, we have gained new knowledge and developed cutting-edge skills in the areas of entomology, molecular biology and genetics, allowing us to sustain a colony containing both local and genetically modified mosquitoes. This research was made possible thanks to an authorisation from the Malian Ministry of Environment, Sanitation and Sustainable Development (MEADD) issued on 21 June 2019 to import a strain of non gene drive genetically modified sterile male mosquitoes and study them in a contained environment. Initially designed at Imperial College London1, the genetically modified mosquitoes were then tested at Polo d’Innovazione di Genomica, Genetica e Biologia (PoloGGB) in Terni, Italy, before being transported to Mali. The mosquito eggs arrived by plane on 4 September 2019. They were kept in the insectarium renovated by the Target Malaria project.
Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modeling study
19134S. Leung, N. Windbichler, E. Wenger, C. Bever and P. Selvaraj, bioRxiv, 2021.11.01.466856. 2021-11-03 14:42:23.
Genetically engineering mosquitoes is a promising new vector control strategy to reinvigorate the fight against malaria in Sub-Saharan Africa. Using an agent-based model of malaria transmission with vector genetics, we examine the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission and quantify the gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting. We evaluate the performance of two different gene drive systems: "classic" and "integral". Various transmission regimes (low, moderate, and high - corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare seeking, are also simulated. Local elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above approximately 80-90‰). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as approximately 50‰ and in high transmission regimes with transmission-blocking effectiveness values above approximately 80-90‰. Thus, a single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.Competing Interest StatementThe authors have declared no competing interest.
Prevalence and molecular characterization of Wolbachia in field-collected Aedes albopictus, Anopheles sinensis, Armigeres subalbatus, Culex pipiens and Cx. tritaeniorhynchus in China
19078Y. Yang, Y. He, G. Zhu, J. Zhang, Z. Gong, S. Huang, G. Lu, Y. Peng, Y. Meng, X. Hao, C. Wang, J. Sun and S. Shang, PLOS Neglected Tropical Diseases, 15:e0009911. 2021-10-29 20:41:21.
Wolbachia are maternally transmitted intracellular bacteria that can naturally and artificially infect arthropods and nematodes. Recently, they were applied to control the spread of mosquito-borne pathogens by causing cytoplasmic incompatibility (CI) between germ cells of females and males. The ability of Wolbachia to induce CI is based on the prevalence and polymorphism of Wolbachia in natural populations of mosquitoes. In this study, we screened the natural infection level and diversity of Wolbachia in field-collected mosquitoes from 25 provinces of China based on partial sequence of Wolbachia surface protein (wsp) gene and multilocus sequence typing (MLST). Among the samples, 2489 mosquitoes were captured from 24 provinces between July and September, 2014 and the remaining 1025 mosquitoes were collected month-by-month in Yangzhou, Jiangsu province between September 2013 and August 2014. Our results showed that the presence of Wolbachia was observed in mosquitoes of Aedes albopictus (97.1%, 331/341), Armigeres subalbatus (95.8%, 481/502), Culex pipiens (87.0%, 1525/1752), Cx. tritaeniorhynchus (17.1%, 14/82), but not Anopheles sinensis (n = 88). Phylogenetic analysis indicated that high polymorphism of wsp and MLST loci was observed in Ae. albopictus mosquitoes, while no or low polymorphisms were in Ar. subalbatus and Cx. pipiens mosquitoes. A total of 12 unique mutations of deduced amino acid were identified in the wsp sequences obtained in this study, including four mutations in Wolbachia supergroup A and eight mutations in supergroup B. This study revealed the prevalence and polymorphism of Wolbachia in mosquitoes in large-scale regions of China and will provide some useful information when performing Wolbachia-based mosquito biocontrol strategies in China.
Spatial modelling for population replacement of mosquito vectors at continental scale
18861N. J. Beeton, A. Wilkins, A. Ickowicz, K. R. Hayes and G. R. Hosack, bioRxiv, 2021.10.06.463299. 2021-10-06 18:41:08.
We explore transmission of the gene drive between the subspecies, different hybridisation mechanisms, the effects of both local dispersal and potential wind-aided migration to the spread, and the development of resistance to the gene drive. We find that given best current available knowledge on the subspecies’ life histories, an introduced gene drive system with typical characteristics can plausibly spread from even distant offshore islands to the African mainland with the aid of wind-driven migration, with resistance taking over within a decade. Our model demonstrates a range of realistic dynamics including the effect of prevailing wind on spread and spatio-temporally varying carrying capacities for subspecies. We thus show both the plausibility and importance of accounting for a wide range of mechanisms from regional to continental scales
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.
Mosquito transgenesis for malaria control
18284S. Dong, Y. Dong, M. L. Simões and G. Dimopoulos, Trends in Parasitology, 2021-09-02 14:42:32.
Malaria is one of the deadliest diseases. Because of the ineffectiveness of current malaria-control methods, several novel mosquito vector-based control strategies have been proposed to supplement existing control strategies. Mosquito transgenesis and gene drive have emerged as promising tools for preventing the spread of malaria by either suppressing mosquito populations by self-destructing mosquitoes or replacing mosquito populations with disease-refractory populations. Here we review the development of mosquito transgenesis and its application for malaria control, highlighting the transgenic expression of antiparasitic effector genes, inactivation of host factor genes, and manipulation of miRNAs and lncRNAs. Overall, from a malaria-control perspective, mosquito transgenesis is not envisioned as a stand-alone approach; rather, its use is proposed as a complement to existing vector-control strategies.
Genetically changed mosquitoes could transform Africa’s long fight against malaria
18258L. Singh, ForumIAS, 2021-08-30 13:13:44.
In nature, there’s a phenomenon called gene drive which operates in the process of reproduction. This is when a genetic element is able to increase the chance that it will be inherited by offspring. The general underlying principle of all gene drives is an organism that will produce offspring similar to themselves. Some characteristics are randomly passed on from parents to the next generation. However, gene drive forces a different type of inheritance that ensures a specific characteristic is always present in the next generation. Scientists engineer gene drive using various molecular tools. Gene drive is not just a human invention; some occur naturally in insects. Unlike traditional genetic modification, gene drives enable extremely rapid spread of the desired characteristics.
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
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).
Genetic engineering may rid world of malaria-transmitting mosquitoes
18163Y. Steinbuch, New York Post, 2021-07-29 14:35:51.
Scientists have eradicated a population of malaria-transmitting mosquitoes by using genetic engineering to make the females infertile — in what the lead researcher called a possible “game-changer in bringing about malaria elimination.” A team of researchers — led by scientists at Imperial College London, Italy’s Polo Genomics Genetics and Biology, and the Liverpool School of Tropical Medicine — used the “gene drive” technology for the study, which was published in Nature Communications. “Gene drive is a self-sustaining and fast-acting technology that can work alongside existing tools such as bed nets, insecticides and vaccines — and could be a game-changer in bringing about malaria elimination,” Andrew Hammond, a molecular biologist at Imperial College London, told the Guardian. Using the technology, scientists may circumvent natural selection by providing genetic instructions that will spread through a mosquito population and pass on a particular trait — in this case, infertility — much faster than could be attained through regular selective breeding, the outlet said.
Gene-Drive Technology Could Decimate Malaria-Carrying Mosquitoes–Scientists Use CRISPR to Modify the Insects’ Genes
17925J. Henry, Tech Times, 2021-07-28 17:53:43.
Gene-drive technology can now suppress the growing numbers of mosquitoes that carry malaria. A group of researchers discovered that this gene-editing technique can eradicate the vectors that could rapidly populate in a particular environment. A mosquito (Anopheles albimanus) is prepared to be studied in a laboratory at the Center for Scientific Research Caucaseco in the outskirts of Cali, Colombia, on April 25, 2012, during the World Day for the fight against malaria. After Colombian physician Manuel Elkin Patarroyo developed a vaccine against malaria in 1986, Colombian scientists keep researching for another immunization for the illness, which in 2010 caused over 855.000 deaths all over the world. A team of 40 scientists is preparing to begin the second phase of chemical tests for a synthetic vaccine against malaria. Malaria is caused by the Plasmodium vivax and Plasmodium falcitarum parasites, and is transmitted by mosquitoes. In a study entitled "Gene-drive suppression of mosquito populations in large cages as a bridge between lab and field" published on Wednesday, July 28 on Nature.com, scientists used genetic engineering to create a special class of mosquitoes that would exterminate those that carry malaria.According to the researchers, their main aim is to develop a weapon that would lessen or wipe out the malaria-spreading mosquitoes. Most importantly, they applied the DNA sequence called "gene drive" to the male mosquitoes. Ruth Muller, one of the researchers who is an entomologist at PoloGGB, said that what they did was a "big breakthrough" in science. Somehow, the scientists are also thinking of freeing the genetically modified mosquitoes someday, but it would take some time to ensure that it is applicable.
Malaria-carrying mosquitoes could be bred out of existence using ‘gene drive’ technology
17923A. Wilkins, METRO, 2021-07-28 17:49:56.
Malaria-carrying mosquitoes have been eliminated using ‘gene drive’ technology in a nature-like environment, in a world-first study. By altering a gene that blocks female mosquito reproduction, and allowing that gene to spread, researchers found they could ensure complete mosquito population collapse within one year of the experiment’s start. It’s the first time so-called ‘gene drive’ technology has been shown to be effective in challenging ecological conditions over a long time scale. The results of the study, published in Nature Communications today, could be a key tool in battling the hundreds of millions of cases of malaria infections that happen each year. ‘The challenges facing malaria elimination have intensified in recent years, due in part to the spread of insecticide resistance and large gaps in funding for parts of sub-Saharan Africa,’ said co-lead author of the study Dr. Drew Hammond. ‘Sadly, researchers estimate that Covid-19 related disruptions may have doubled mortality from malaria in 2020, threatening a setback of several decades. ‘Gene drive is a self-sustaining and fast acting technology that can work alongside existing tools such as bed nets, insecticides and vaccines – and could be a game-changer in bringing about malaria elimination.’
Scientists reveal controversial genetically modified mosquitoes in high-security lab
17920The Frontier Post, The Frontier Post, 2021-07-28 17:44:04.
Many years of additional research will be needed to prove the approach works and the mosquitoes would be safe to release into the wild. The project would also require regulatory approval and agreement by local residents in areas where those mosquitoes live, mostly in sub-Saharan Africa and parts of Asia. Despite years of efforts, malaria remains a major health problem. The mosquito-borne parasitic disease sickens more than 200 million people every year and kills more than 400,000, many of whom are children. So Muller and her colleagues decided to use CRISPR, a technique that enables scientists to easily make very precise changes in DNA to genetically modify the Anopheles gambiae species of mosquito, which spreads malaria in sub-Saharan Africa. The modification consisted of a mutation in a gene known as “doublesex,” which female mosquitoes need for normal development. The mutation deforms their mouths, making them unable to bite and spread the parasite. It also deforms their reproductive organs, rendering them unable to lay eggs. The mutation is combined with a gene drive, “effectively a selfish type of genetic element that spreads itself in the mosquito population,” says Tony Nolan of the Liverpool School of Tropical
Genetic engineering test with mosquitoes ‘may be game changer’ in eliminating malaria
17918L. Geddes, The Guardian, 2021-07-28 17:38:58.
Scientists have successfully wiped out a population of malaria-transmitting mosquitoes by using a radical form of genetic engineering to render the females infertile – in the most advanced and largest ever test of use of the technology to fight the disease. As well as bringing fresh hope in the fight against one of the world’s biggest killers, the study lays the foundations for further trials of gene-drive technology, which could mean self-destroying mosquitoes being released into the wild within 10 years. “This is a very exciting development,” said Dr Thomas Price, a senior lecturer in evolution, ecology and behaviour at the University of Liverpool, who was not involved in the research. “There are still lots of ethical and regulatory questions that need answering. But none of those really matter if it is impossible to build gene drives that are effective in the field. This is a major step towards achieving that.” Despite the reduction in malaria over recent decades there were still 229m cases of the disease in 2019, and 409,000 deaths. Dr Drew Hammond, at Imperial College London, who led the new research, said: “Gene drive is a self sustaining and fast acting technology that can work alongside existing tools such as bed nets, insecticides and vaccines, and could be a game changer in bringing about malaria elimination.”
How An Altered Strand Of DNA Can Cause Malaria-Spreading Mosquitoes To Self-Destruct
17862R. Stein, NPR, 2021-07-28 15:19:15.
For the first time, scientists have shown that a new kind of genetic engineering can crash populations of malaria-spreading mosquitoes. In the landmark study, published Wednesday in the journal Nature Communications, researchers placed the genetically modified mosquitoes in a special laboratory that simulated the conditions in sub-Saharan Africa, where they spread the deadly disease. The male mosquitoes were engineered with a sequence of DNA known as a "gene drive" that can rapidly transmit a deleterious mutation that essentially wipes out populations of the insects. The goal is to create a powerful new tool to fight malaria, which remains one of the world's most terrible scourges. "Our study is the first [that] could show that gene-drive technology works under ecologically challenging conditions," says Ruth Muller, an entomologist who led the research at PoloGGB, a high-security lab in Terni, Italy. "This is the big breakthrough that we made with our study."
A lab experiment shows that we could engineer malaria-carrying mosquitoes to kill themselves off
17909A. Micu, ZME Science, 2021-07-28 15:17:37.
A new paper showcases how genetic engineering can be used to cause populations of malaria-spreading mosquitoes to self-destroy. An international research effort has shown, in the context of a lab experiment, that male mosquitoes engineered to carry a certain strand of DNA can rapidly destroy entire groups of these blood-sucking insects. The main importance of this experiment is that it showcases that gene-drive technology can be used even in harsh environmental conditions, such as those in sub-Saharan Africa. This “gene drive” sequence is essentially a damaging mutation that could prove to be a powerful tool against the carriers of malaria.
Malarial mosquitoes suppressed in experiments that mimic natural environments
17903H. Dunning, Phys Org, 2021-07-28 14:58:38.
Researchers have shown "gene drive" technology, which spreads a genetic modification blocking female reproduction, works in natural-like settings. The team, led by researchers from Imperial College London, Polo GGB and Liverpool School of Tropical Medicine were able to suppress populations of a malaria-carrying mosquito in a year-long experiment mimicking natural environments. This is the first time a gene drive has been shown to be as effective as expected when tested in challenging ecological conditions over a long timescale. The results are published today in Nature Communications. Despite the reduction in malaria over recent decades, there were still 229 million cases of malaria in 2019—an increase on the previous year—and 409,000 deaths. Co-lead author of the study Dr. Drew Hammond, from the Department of Life Sciences at Imperial College London and the Johns Hopkins Malaria Research Institute, said: "The challenges facing malaria elimination have intensified in recent years, due in part to the spread of insecticide resistance and large gaps in funding for parts of sub-Saharan Africa.
Horizontal Transmission of the Symbiont Microsporidia MB in Anopheles arabiensis
17856G. Nattoh, T. Maina, E. E. Makhulu, L. Mbaisi, E. Mararo, F. G. Otieno, T. Bukhari, T. O. Onchuru, E. Teal, J. Paredes, J. L. Bargul, D. M. Mburu, E. A. Onyango, G. Magoma, S. P. Sinkins and J. K. Herren, Frontiers in Microbiology, 12. 2021-07-28 13:43:29.
The recently discovered Anopheles symbiont, Microsporidia MB, has a strong malaria transmission-blocking phenotype in Anopheles arabiensis, the predominant Anopheles gambiae species complex member in many active transmission areas in eastern Africa. The ability of Microsporidia MB to block Plasmodium transmission together with vertical transmission and avirulence makes it a candidate for the development of a symbiont-based malaria transmission blocking strategy. We investigate the characteristics and efficiencies of Microsporidia MB transmission between An. arabiensis mosquitoes. We show that Microsporidia MB is not transmitted between larvae but is effectively transmitted horizontally between adult mosquitoes. Notably, Microsporidia MB was only found to be transmitted between male and female An. arabiensis, suggesting sexual horizontal transmission. In addition, Microsporidia MB cells were observed infecting the An. arabiensis ejaculatory duct. Female An. arabiensis that acquire Microsporidia MB horizontally are able to transmit the symbiont vertically to their offspring. We also investigate the possibility that Microsporidia MB can infect alternate hosts that live in the same habitats as their An. arabiensis hosts, but find no other non-anopheline hosts. Notably, Microsporidia MB infections were found in another primary malaria African vector, Anopheles funestus s.s. The finding that Microsporidia MB can be transmitted horizontally is relevant for the development of dissemination strategies to control malaria that are based on the targeted release of Microsporidia MB infected Anopheles mosquitoes.
Gene-drive suppression of mosquito populations in large cages as a bridge between lab and field
17853A. Hammond, P. Pollegioni, T. Persampieri, A. North, R. Minuz, A. Trusso, A. Bucci, K. Kyrou, I. Morianou, A. Simoni, T. Nolan, R. Müller and A. Crisanti, Nature Communications, 12:4589. 2021-07-28 12:31:16.
CRISPR-based gene-drives targeting the gene doublesex in the malaria vector Anopheles gambiae effectively suppressed the reproductive capability of mosquito populations reared in small laboratory cages. To bridge the gap between laboratory and the field, this gene-drive technology must be challenged with vector ecology.Here we report the suppressive activity of the gene-drive in age-structured An. gambiae populations in large indoor cages that permit complex feeding and reproductive behaviours.The gene-drive element spreads rapidly through the populations, fully supresses the population within one year and without selecting for resistance to the gene drive. Approximate Bayesian computation allowed retrospective inference of life-history parameters from the large cages and a more accurate prediction of gene-drive behaviour under more ecologically-relevant settings. Generating data to bridge laboratory and field studies for invasive technologies is challenging. Our study represents a paradigm for the stepwise and sound development of vector control tools based on gene-drive.
Resistance to a CRISPR-based gene drive at an evolutionarily conserved site is revealed by mimicking genotype fixation
17940S. Fuchs, W. Garrood, A. Beber, A. Hammond, R. Galizi, M. Gribble, G. Morselli, T.-Y. Hui, K. Willis, N. Kranjc, A. Burt, T. Nolan and A. Crisanti, bioRxiv, 2021-07-26 13:48:52.
CRISPR-based homing gene drives can be designed to disrupt essential genes whilst biasing their own inheritance, leading to suppression of mosquito populations in the laboratory. This class of gene drives relies on CRISPR-Cas9 cleavage of a target sequence and copying (‘homing’) therein of the gene drive element from the homologous chromosome. However, target site mutations that are resistant to cleavage yet maintain the function of the essential gene are expected to be strongly selected for. Targeting functionally constrained regions where mutations are not easily tolerated should lower the probability of resistance. Evolutionary conservation at the sequence level is often a reliable indicator of functional constraint, though the actual level of underlying constraint between one conserved sequence and another can vary widely. Here we generated a novel gene drive in the malaria vector Anopheles gambiae , targeting an ultra-conserved target site in a haplosufficient essential gene (AGAP029113) required during mosquito development, which fulfils many of the criteria for the target of a population suppression gene drive. We then designed a selection regime to experimentally assess the likelihood of generation and subsequent selection of gene drive resistant mutations at its target site. We simulated, in a caged population, a scenario where the gene drive was approaching fixation, where selection for resistance is expected to be strongest. Continuous sampling of the target locus revealed that a single, restorative, in-frame nucleotide substitution was selected. Our findings show that ultra-conservation alone need not be predictive of a site that is refractory to target site resistance. Our strategy to evaluate resistance in vivo could help to validate candidate gene drive targets for their resilience to resistance and help to improve predictions of the invasion dynamics of gene drives in field populations. <h4>Author summary</h4> Gene drives have the potential to be applied as novel control strategy of disease-transmitting mosquitoes, by spreading genetic traits that suppress or modify the target population. Many gene drive elements work by recognising and cutting a specific target sequence in the mosquito genome and copying themselves into that target sequence allowing the gene drive to increase in frequency in the population. Like other mosquito control interventions, efficacy will greatly depend on minimising the development of resistance to the gene drive mechanism - most likely via a change in the target sequence that prevents further cutting. One strategy to reduce resistance is to target sequences that are highly conserved, which implies that changes cannot easily be tolerated. We developed a strategy that simulates high selection pressure, under which resistance is most likely to emerge, and therefore provides a stringent test of its propensity to arise. Unlike previous results with another gene drive, we recovered a resistant allele within a few generations of gene drive exposure and at high frequency. Our results show that conserved sequences can vary hugely in ability to tolerate mutations and highlights the need to functionally validate future candidate gene drive target sites for their robustness to resistance.
Part of ‘master plan’: Researchers receive grant to fund research on malaria
17748L. Huang, The Daily Californian, 2021-07-11 13:33:25.
Early this month, The Marshall Lab at UC Berkeley received an $800,000 grant from the Bill and Melinda Gates Foundation to fund its research on genetics-based malaria mosquito control. The Marshall Lab is one of many teams playing a part in the Gates Foundation’s decades-long “master plan” to eradicate malaria, according to associate professor John Marshall, the project’s principal investigator. Based on data from the World Health Organization, malaria kills hundreds of thousands of people a year. The lab has focused on malaria prevention ever since it opened its doors in 2015, publishing work about mosquito intervention and control mechanisms related to genetic mathematical modeling. “If you have a drug to control malaria or a mosquito net, then how that is implemented on a continental scale is more than a problem of having the intervention itself — you need to think about the numbers involved,” Marshall said. Marshall compared mosquitoes to humans in that they have similar genetic makeups. He said some mosquito genes can be altered to either prevent disease transmission to humans or reduce rates of mosquito reproduction. Marshall’s team plans to apply its Mosquito Gene Drive Explorer, which simulates releases of genetically modified mosquitoes into habitats, to aid fellow researchers funded by the Gates Foundation. With the system, researchers can identify the efficacy of systems for reducing cases of malaria in order to pinpoint which characteristics of gene constructs can be prioritized to most efficiently suppress the disease.
Africa Turning to Gene Drive Technology for Malaria Elimination
17669M. Hearty, Science Africa, 2021-07-09 20:02:22.
With Africa accounting for nine out of ten malaria cases globally, the continent is turning to gene drive technology to control the disease. This is according to a decision made by African leaders at the 29th Summit of Heads of States and Governments of the African Union held in Addis Ababa. There are 3500 to 4000 mosquito species worldwide and 837 of the species are in Africa, with only 3 species transmitting malaria in sub-Saharan Africa. Speaking during a virtual conference by the African Union Development Agency (AUDA-NEPAD) , Dr Abdoulaye Diabate, Head of Medical Entomology and Parasitology at the Research Institute in health Sciences in Burkina Faso who presented on Gene Drive for Malaria Control and Elimination in Africa said that two options for genetic control of mosquito-borne infectious diseases identified were population suppression and population replacement. “Population suppression involves releasing of modified mosquitoes into the population, and this can cause transient or permanent suppression. With the population replacement method, modified mosquitoes released into the population can lead to the spread of a gene that blocks malaria transmission,” the Medical Entomologist stated.
A new tool in the global fight against malaria
17666S. Laux, Brighter World, 2021-07-08 19:56:20.
McMaster researchers with the Institute on Ethics & Policy for Innovation (IEPI) have played a key role in developing updated international guidelines that will inform research and development on genetically modified mosquitoes – an initiative that could significantly affect global efforts to eradicate mosquito-borne illnesses such as dengue fever, Zika virus and malaria. Released by the World Health Organization in late May, the guidelines describe best practices to ensure that the study of genetically modified mosquitoes is scientifically rigorous and meets essential standards of safety, effectiveness, accessibility and ethics. “The previous World Health Organization guidance for testing genetically modified mosquitoes was from 2014 – and since then, there have been multiple technological developments and considerable scientific progress,” explains Claudia Emerson, the director of IEPI and a professor of philosophy who, along with IEPI researchers Travis Ramsay and Aaron Roberts, developed the guidance’s chapter on ethical considerations. “Genetically modifying organisms isn’t new, at least not from an ethical or scientific perspective – but as the technology has developed over the years, especially with respect to mosquitoes, there has been a change in its perception and the receptivity to using it. It was important to update the guidance to reflect these changes.”
Marshall Lab receives Gates grant for genetics-based malaria mosquito control
17654Berkeley Public Health, Berkeley Public Health, 2021-07-08 19:33:19.
Berkeley Public Health Associate Professor John Marshall, PhD, and Assistant Project Scientist Héctor Sánchez, PhD, have received an $800,000 grant from the Bill & Melinda Gates Foundation to support their lab’s work in genetics-based malaria mosquito control. Malaria, the most devastating mosquito-borne disease, poses a major public health burden throughout much of the world. Novel genetics-based tools that can be shown to be safe and effective would be transformative in eliminating the disease and the suffering it causes. “Malaria continues to be exceptionally difficult to eliminate with currently-available tools,” said Marshall. “Insecticide-treated nets and antimalarial drugs have succeeded in reducing the African malaria burden by about a half, but their impact has stagnated in recent years and new tools are needed. There is now growing recognition that the most promising new tools for malaria elimination are vaccines and gene-edited mosquitoes.”
Fighting disease: How are genetically engineered mosquitoes regulated?
17652A. Julie, Global News, 2021-07-08 19:26:36.
Mosquitoes have long been associated with the spread of diseases like malaria, dengue fever and the Zika virus. But scientists around the world have been exploring the possibility that mosquitoes could also be key to slowing the spread of disease. By genetically altering the DNA of mosquitoes, scientists hope to prevent them from passing on pathogens to humans and, therefore, control the spread of vector-borne diseases. To some, it is an exciting opportunity that could open up new possibilities in the fight against endemic diseases. But the practice has also raised questions from some in the scientific and environmental communities about the impact on local ecosystems, and the ripple effects such modifications could have on the mosquito populations themselves.
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.
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.
Using gene drives to control malaria
17594A. Fell, Daily News, 2021-06-25 14:08:33.
A group of UC scientists led by Greg Lanzaro, professor of pathology, microbiology and immunology in the UC Davis School of Veterinary Medicine, recently completed an analysis of a strategy aimed at eliminating malaria from Africa using genetically engineered mosquitoes. Lanzaro’s lab is part of the UC Irvine Malaria Initiative. The laboratories of Anthony James at UC Irvine and Ethan Bier at UC San Diego engineered mosquitoes with synthetic genes that render them incapable of transmitting the malaria parasite and coupled these genes with a CRISPR-Cas9 gene drive to promote their spread into malaria vector populations in Africa. The idea is to ‘drive’ the new malaria-resistance genes into the mosquito population at a much higher rate than could occur naturally.
Population modification strategies for malaria vector control are uniquely resilient to observed levels of gene drive resistance alleles
17502G. C. Lanzaro, H. M. Sánchez C, T. C. Collier, J. M. Marshall and A. A. James, BioEssays, 2021-06-20 13:46:45.
Cas9/guide RNA (gRNA)-based gene drive systems are expected to play a transformative role in malaria elimination efforts., whether through population modification, in which the drive system contains parasite-refractory genes, or population suppression, in which the drive system induces a severe fitness load resulting in population decline or extinction. DNA sequence polymorphisms representing alternate alleles at gRNA target sites may confer a drive-resistant phenotype in individuals carrying them. Modeling predicts that, for observed levels of SGV at potential target sites and observed rates of de novo DRA formation, population modification strategies are uniquely resilient to DRAs. We conclude that gene drives can succeed when fitness costs incurred by drive-carrying mosquitoes are low enough to prevent strong positive selection for DRAs produced de novo or as part of the SGV and that population modification strategies are less prone to failure due to drive resistance.
Stable high-density and maternally inherited Wolbachia infections in Anopheles moucheti and Anopheles demeilloni mosquitoes
17504T. Walker, S. Quek, C. L. Jeffries, J. Bandibabone, V. Dhokiya, R. Bamou, M. Kristan, L. A. Messenger, A. Gidley, E. A. Hornett, E. R. Anderson, C. Cansado-Utrilla, S. Hegde, C. Bantuzeko, J. C. Stevenson, N. F. Lobo, S. C. Wagstaff, C. A. Nkondjio, S. R., Current Biology, 31:2310. 2021-06-14 13:55:55.
Wolbachia, a widespread bacterium that can reduce pathogen transmission in mosquitoes, has recently been reported to be present in Anopheles (An.) species. In wild populations of the An. gambiae complex, the primary vectors of Plasmodium malaria in Sub-Saharan Africa, Wolbachia DNA sequences at low density and infection frequencies have been detected. As the majority of studies have used highly sensitive nested PCR as the only method of detection, more robust evidence is required to determine whether Wolbachia strains are established as endosymbionts in Anopheles species. Here, we describe high-density Wolbachia infections in geographically diverse populations of An. moucheti and An. demeilloni. Fluorescent in situ hybridization localized a heavy infection in the ovaries of An. moucheti, and maternal transmission was observed. Genome sequencing of both Wolbachia strains obtained genome depths and coverages comparable to those of other known infections. Notably, homologs of cytoplasmic incompatibility factor (cif) genes were present, indicating that these strains possess the capacity to induce the cytoplasmic incompatibility phenotype, which allows Wolbachia to spread through host populations. These strains should be further investigated as candidates for use in Wolbachia biocontrol strategies in Anopheles aiming to reduce the transmission of malaria.
Vector control: Discovery of Wolbachia in malaria vectors
17554P. A. Ross and A. A. Hoffmann, Current Biology, 31:R738-R740. 2021-06-07 14:28:04.
Wolbachia bacteria are being widely released for suppression of dengue transmitted by Aedes mosquitoes. Walker, Quek, Jeffries and colleagues present robust evidence for natural Wolbachia infections in malaria-vectoring Anopheles mosquitoes, paving the way for new Wolbachia-based intervention
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.
Improving mosquito control strategies with population genomics
18781T. L. Schmidt, N. M. Endersby-Harshman and A. A. Hoffmann, Trends in Parasitology, 37:907-921. 2021-05-29 12:41:38.
Mosquito control strategies increasingly apply knowledge from population genomics research. This review highlights recent applications to three research domains: mosquito invasions, insecticide resistance evolution, and rear and release programs. Current research trends follow developments in reference assemblies, either as improvements to existing assemblies (particularly Aedes) or assemblies for new taxa (particularly Anopheles). With improved assemblies, studies of invasive and rear and release target populations are better able to incorporate adaptive as well as demographic hypotheses. New reference assemblies are aiding comparisons of insecticide resistance across sister taxa while helping resolve taxon boundaries amidst frequent introgression. Anopheles gene drive deployments and improved Aedes genome assemblies should lead to a convergence in research aims for Anopheles and Aedes in the coming years.
The origin of island populations of the African malaria mosquito, Anopheles coluzzii
17287M. Campos, M. Hanemaaijer, H. Gripkey, T. C. Collier, Y. S. Lee, A. J. Cornel, J. Pinto, D. Ayala, H. Rompao and G. C. Lanzaro, Communications Biology, 4:9. 2021-05-26 10:26:11.
Anopheles coluzzii is a major malaria vector throughout its distribution in west-central Africa. Here we present a whole-genome study of 142 specimens from nine countries in continental Africa and three islands in the Gulf of Guinea. This sample set covers a large part of this species' geographic range. Our population genomic analyses included a description of the structure of mainland populations, island populations, and connectivity between them. Three genetic clusters are identified among mainland populations and genetic distances (F-ST) fits an isolation-by-distance model. Genomic analyses are applied to estimate the demographic history and ancestry for each island. Taken together with the unique biogeography and history of human occupation for each island, they present a coherent explanation underlying levels of genetic isolation between mainland and island populations. We discuss the relationship of our findings to the suitability of Sao Tome and Principe islands as candidate sites for potential field trials of genetic-based malaria control strategies. Campos, Lanzaro and colleagues use whole-genome sequencing and population genomic analyses to infer connectivity between mainland and island mosquito populations in West Africa. The unique biogeographic history for each island population is reported, and the findings highlight potential candidate sites for genetic-based malaria control strategies.
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.
A natural symbiotic bacterium drives mosquito refractoriness to Plasmodium infection via secretion of an antimalarial lipase
17027H. Gao, L. Bai, Y. M. Jiang, W. Huang, L. L. Wang, S. G. Li, G. D. Zhu, D. Q. Wang, Z. H. Huang, X. S. Li, J. Cao, L. B. Jiang, M. Jacobs-Lorena, S. Zhan and S. B. Wang, Nature Microbiology, 25. 2021-05-06 11:00:53.
The stalling global progress in the fight against malaria prompts the urgent need to develop new intervention strategies. Whilst engineered symbiotic bacteria have been shown to confer mosquito resistance to parasite infection, a major challenge for field implementation is to address regulatory concerns. Here, we report the identification of a Plasmodium-blocking symbiotic bacterium, Serratia ureilytica Su_YN1, isolated from the midgut of wild Anopheles sinensis in China that inhibits malaria parasites via secretion of an antimalarial lipase. Analysis of Plasmodium vivax epidemic data indicates that local malaria cases in Tengchong (Yunnan province, China) are significantly lower than imported cases and importantly, that the local vector A. sinensis is more resistant to infection by P. vivax than A. sinensis from other regions. Analysis of the gut symbiotic bacteria of mosquitoes from Yunnan province led to the identification of S. ureilytica Su_YN1. This bacterium renders mosquitoes resistant to infection by the human parasite Plasmodium falciparum or the rodent parasite Plasmodium berghei via secretion of a lipase that selectively kills parasites at various stages. Importantly, Su_YN1 rapidly disseminates through mosquito populations by vertical and horizontal transmission, providing a potential tool for blocking malaria transmission in the field. The symbiotic bacterium Serratia ureilytica can disseminate through mosquito populations and render mosquitoes resistant to Plasmodium infection by secreting an antimalarial lipase.
Selection of Sites for Field Trials of Genetically Engineered Mosquitoes with Gene Drive
16932G. C. Lanzaro, M. Campos, M. Crepeau, A. Cornel, A. Estrada, H. Gripkey, Z. Haddad, A. Kormos, S. Palomares and W. Sharpee, bioRxiv, 2021.04.28.441877. 2021-04-28 15:53:05.
Novel malaria control strategies using genetically engineered mosquitoes (GEMs) are on the horizon. Population modification is one approach wherein mosquitoes are engineered with genes rendering them refractory to the malaria parasite coupled with a low-threshold, Cas9-based gene drive. When released into a wild vector population, GEMs preferentially transmit these beneficial genes to their offspring, ultimately modifying a vector population into a non-vector one. Deploying this technology awaits evaluation including ecologically contained field trials. Here, we consider a process for site selection, the first critical step in designing a trial. Our goal is to identify a site that maximizes prospects for success, minimizes risk, and serves as a fair, valid, and convincing test of efficacy and impacts of a GEM product intended for large-scale deployment in Africa. We base site selection on geographical, geological, and biological, rather than social or legal, criteria. We recognize the latter as critically important but not preeminent. We propose physical islands as being the best candidates for a GEM field trial and present an evaluation of 22 African islands. We consider geographic and genetic isolation, biological complexity, island size, topography, and identify two island groups that satisfy key criteria for ideal GEM field trial sites.Competing Interest StatementThe authors have declared no competing interest.
“Maskandi experience”: exploring the use of a cultural song for community engagement in preparation for a pilot Sterile Insect Technique release programme for malaria vector control in KwaZulu-Natal Province, South Africa 2019
17029P. N. Manana, S. Jewett, J. Zikhali, D. Dlamini, N. Mabaso, Z. Mlambo, R. Ngobese and G. Munhenga, Malaria Journal, 20:11. 2021-04-28 11:06:19.
Background An assessment of the Sterile Insect Technique (SIT) as a complementary malaria vector control tool, is at an advanced stage in South Africa. The technique involves the release of laboratory-reared sterilized male mosquitoes of the major malaria vector Anopheles arabiensis, raising social, ethical and regulatory concerns. Therefore, its implementation largely depends on community participation and acceptance. Against this background, it is critical that robust and effective community strategies are developed. This study describes the development of a cultural song to engage the community and increase awareness on SIT and malaria control in KwaZulu-Natal, South Africa. Methods An exploratory concurrent mixed-methods study was conducted to get opinions about the effectiveness of a cultural song developed to engage communities and increase acceptability of the SIT technology. Two self-administered surveys (expert and community) were conducted. Additionally, more in depth opinions of the song and its effectiveness in conveying the intended information were investigated through three community dialogue sessions with community members in the study area. Results A total of 40 experts and 54 community members participated in the survey. Four themes were identified in relation to the appropriateness and effectiveness of the song, with a fifth theme focused on recommendations for adaptations. Overall, the song was well received with the audience finding it entertaining and informative. Responses to unstructured questions posed after the song showed an increase in the knowledge on malaria transmission and SIT technology. In particular, the explanation that male mosquitoes do not bite allayed anxiety and fears about the SIT technology. Conclusion The song was deemed both culturally appropriate and informative in engaging community members about the SIT technology. It proved useful in promoting health messages and conveying SIT technology as a complementary malaria vector control tool. With minor adaptations, the song has potential as an area-wide community engagement tool in areas targeted for sterile male releases.
Estimates of the population size and dispersal range of Anopheles arabiensis in Northern KwaZulu-Natal, South Africa: implications for a planned pilot programme to release sterile male mosquitoes
17062M. L. Kaiser, O. R. Wood, D. Damiens, B. D. Brooke, L. L. Koekemoer and G. Munhenga, Parasites and Vectors, 14:18. 2021-04-19 13:57:18.
The Anopheles gambiae complex and An. funestus group species made up the majority of wild collections along with other anophelines. The An. arabiensis population size was estimated to be between 550 and 9500 males per hectare depending on time of year, weather conditions and method used. Average dispersal distance of marked males ranged from 58 to 86 m. Marked males were found in swarms with wild males, indicating that laboratory-reared males are able to locate and participate in mating swarms. Conclusions It was logistically feasible to conduct mark-release-recapture studies at the current scale. The population size estimates obtained may provide a guideline for the initial number of males to use for a pending SIT pilot trial. It is promising for future SIT trials that laboratory-reared marked males participated in natural swarms, appearing at the right place at the right time.
Breeding Malaria Out: Scientists Engineer Mosquitos to Spread Antimalaria Genes
16800L. Papadopoulos, INTERSTING ENGINEERING, 2021-04-17 13:57:17.
According to the Centers for Disease Control and Prevention (CDC), malaria is a "serious and sometimes fatal disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans." There are four types of malaria parasites: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae with P. falciparum being the one most likely to result in death. But what if these mosquitos could be genetically altered to spread antimalaria genes instead of the disease? That would be nothing short of a miracle. Researchers from Imperial College London have successfully altered a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species. This innovation may result in curbing malaria once and for all. This is especially important as the parasite that causes malaria has been becoming increasingly resistant to antimalarial drugs.
Curbing Malaria’s Spread by Genetic Engineering
16792Anonymous, Genetic Engineering & Biotechnology News, 2021-04-15 13:03:49.
There is an urgent need to find new ways to combat the growing mosquito resistance to pesticides and malaria parasite resistance to antimalarial drugs. Gene drives are being tested as a new approach. In a new study, researchers from the Imperial College London reported that their approach brings gene drives one step closer as a potential strategy for eliminating malaria. Their study was published in the journal eLife, in a paper titled, “Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement.”
New genetic modification could cut malaria spread
16789Staff Writers, MALAYSIA NOW, 2021-04-15 12:56:54.
Altering a mosquito’s gut genes to make them spread antimalarial genes to the next generation of their species shows promise as an approach to curb malaria, suggests a preliminary study published in eLife on Tuesday. The study is the latest in a series of steps being taken toward using CRISPR-Cas9 gene-editing technology to make changes in mosquito genes that could reduce their ability to spread malaria. If further studies support this approach, it could provide a new way to reduce illnesses and deaths caused by malaria. Growing mosquito resistance to pesticides, as well as malaria parasite resistance to antimalarial drugs, has created an urgent need for new ways to fight the disease. Gene drives are being tested as a new approach. They work by creating genetically modified mosquitoes that, when released into the environment, would spread genes that either reduce mosquito populations or make the insects less likely to spread the malaria parasite.
Researchers Using Mutant Mosquitoes To End Malaria, Which Kills 4 Lakh Per Year
16797M. Mohanti, India Times, 2021-04-14 13:20:52.
Every year, more than 22 crore people get infected with malaria and more than 4 lakh die because of it. In fact, in 2019, nearly half of the world's population was at risk of malaria. According to WHO, infants or children aged under 5 years are the most vulnerable group, accounting for two-third of all malaria deaths worldwide. Malaria is caused by parasites that are transmitted to people via the bites of infected female Anopheles mozzies. In a non-immune individual, symptoms--fever, headache, and chills--usually appear 10–15 days after the infective mosquito bite. If it goes untreated for a day, these mild symptoms can progress to severe illness, often leading to death, if bitten by the P. falciparum parasite.
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.
Systematic identification of plausible pathways to potential harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa
16668J. B. Connolly, J. D. Mumford, S. Fuchs, G. Turner, C. Beech, A. R. North and A. Burt, Malaria Journal, 20:170. 2021-03-29 18:49:26.
Population suppression gene drive has been proposed as a strategy for malaria vector control. A CRISPR-Cas9-based transgene homing at the doublesex locus (dsxFCRISPRh) has recently been shown to increase rapidly in frequency in, and suppress, caged laboratory populations of the malaria mosquito vector Anopheles gambiae. Here, problem formulation, an initial step in environmental risk assessment (ERA), was performed for simulated field releases of the dsxFCRISPRh transgene in West Africa.
Detailed genome map of malaria vector
16381The Hindu, Aspirant World, 2021-02-14 15:03:12.
In order to engineer advanced forms of defence against malaria transmission, including targeted CRISPR and gene drive–based strategies, scientists require intricate knowledge of the genomes of vector mosquitoes. CRISPR technology is a gene-editing tool which allows researchers to easily alter DNA sequences and modify gene function.They produced a new reference genome for the Asian malaria vector mosquito Anopheles stephensi.
Researchers Unveil Detailed Genome of Invasive Malaria Mosquito
16374M. Aguilera, UC San Diego News Center, 2021-02-11 20:37:12.
Mosquito-transmitted malaria remains the number one worldwide killer among vector-borne diseases, claiming more than 400,000 human lives in 2019. In order to engineer advanced forms of defense against malaria transmission, including targeted CRISPR and gene drive-based strategies, scientists require intricate knowledge of the genomes of vector mosquitoes. Mahul Chakraborty—a project scientist at the University of California, Irvine, working with colleagues at the Tata Institute for Genetics and Society (TIGS) at UC San Diego and India, and the Institute of Bioinformatics and Applied Biotechnology in Bangalore, India—has produced a groundbreaking new reference genome for the Asian malaria vector mosquito Anopheles stephensi. Full details of the genome, which the scientists say is now on par with the best animal genomes available to science (humans and fruit flies), are published in the journal BMC Biology.
Hidden genomic features of an invasive malaria vector, Anopheles stephensi, revealed by a chromosome-level genome assembly
16376M. Chakraborty, A. Ramaiah, A. Adolfi, P. Halas, B. Kaduskar, L. T. Ngo, S. Jayaprasad, K. Paul, S. Whadgar, S. Srinivasan, S. Subramani, E. Bier, A. A. James and J. J. Emerson, BMC Biology, 19:28. 2021-02-10 20:40:13.
The mosquito Anopheles stephensi is a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis of vectorial capacity and engineering genetic interventions are both impeded by limitations of a vector’s genome assembly. The existing assemblies of An. stephensi are draft-quality and contain thousands of sequence gaps, potentially missing genetic elements important for its biology and evolution.
Experts oppose plan to breed mosquitoes
16279T. Abet, Daily Monitor, 2021-02-01 17:11:29.
Environmentalists have opposed the plan to breed and release genetically modified mosquitoes in the country to curb malaria prevalence. They say the act presents substantial human and environmental health risks. Their objection follows last week’s announcement by scientists at Uganda Virus Research Institute (UVRI) that they have embarked on a series of activities aimed at breeding and releasing genetically modified mosquitoes (GMMs) that could curb malaria transmission.
Genetically modified mosquitoes to curb malaria
16221T. Abet, Daily Monitor, 2021-01-29 16:20:15.
Scientists at Uganda Virus Research Institute (UVRI) have started breeding mosquitoes with the aim of modifying their genetic materials and releasing them to the environment to curb malaria transmission. The genetically modified mosquitoes, according to the scientists, do not transmit malaria parasites when they bite. Dr Jonathan Kayondo, the project lead coordinator at the UVRI, said when the modified male mosquito mates with common mosquitoes, the female off springs are infertile. This, he explained will significantly suppress the population or eliminate mosquitoes thereby stopping malaria transmission and deaths.
New genetically modified mosquitoes to help fight malaria
16216D. Zirimala, Capital Radio FM, 2021-01-29 16:11:15.
According to Dr. Jonathan Kayondo, the principal investigator of the Target Malaria project, the genetically modified mosquitoes do not transmit malaria parasites when they bite. These are made infertile so that when they cross breed with the female anopheles mosquito, they are not able to reproduce. He says with this new research project, they are complimenting the already existing malaria control methods such as insecticides treated mosquito nets, indoor residual spraying and drugs but there is need to get additional tools to help eradicate the disease.
Drivers of mosquito mating
16110N. C. Manoukis, Science, 371:340. 2021-01-22 15:54:49.
Gene drive systems are based on the release of organisms whose genomes have been modified or engineered to spread a desired allele or trait (such as resistance to the parasites that cause malaria) through a population. Success will depend on the release of genetically modified males that will be able to mate with wild females. Beyond gene drive strategies, in mosquitoes it is understood that only males can be released as part of any genetic pest control (GPC) program (7); females feed on blood to lay eggs, and releasing insects that will feed on humans is widely unacceptable.
Clock genes and environmental cues coordinate Anopheles pheromone synthesis, swarming, and mating
16108G. Wang, J. Vega-Rodríguez, A. Diabate, J. Liu, C. Cui, C. Nignan, L. Dong, F. Li, C. O. Ouedrago, A. M. Bandaogo, P. S. Sawadogo, H. Maiga, T. L. Alves e Silva, T. V. Pascini, S. Wang and M. Jacobs-Lorena, Science, 371:411. 2021-01-22 15:35:30.
Knockdown of per and tim expression affects Anopheles gambiae s.s. and Anopheles stephensi male mating in the laboratory, and it reduces male An. coluzzii swarming and mating under semifield conditions. Light and temperature affect mosquito mating, possibly by modulating per and/or tim expression. Moreover, the desaturase gene desat1 is up-regulated and rhythmically expressed in the heads of swarming males and regulates the production of cuticular hydrocarbons, including heptacosane, which stimulates mating activity.
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.
Mosquito population modification: the drive to malaria eradication
15272A. A. James, BugBitten BMC, 2020-11-27 14:37:56.
We have had considerable success in the past demonstrating that we can use modern molecular biological and insect transgenesis tools to make genes that prevent mosquitoes from passing on parasites (see 1 and 2). We have focused most recently on laboratory experiments to find ways to move these genes into wild mosquito populations.
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
Vector-Focused Approaches to Curb Malaria Transmission in the Brazilian Amazon: An Overview of Current and Future Challenges and Strategies
15960E. M. Rocha, R. D. Katak, J. C. de Oliveira, M. D. Araujo, B. C. Carlos, R. Galizi, F. Tripet, O. Marinotti and J. A. Souza, Tropical Medicine and Infectious Disease, 5. 2020-10-20 18:16:39.
Here we present an overview on both conventional and novel promising vector-focused tools to curb malaria transmission in the Brazilian Amazon. If well designed and employed, vector-based approaches may improve the implementation of malaria-control programs, particularly in remote or difficult-to-access areas and in regions where existing interventions have been unable to eliminate disease transmission. However, much effort still has to be put into research expanding the knowledge of neotropical malaria vectors to set the steppingstones for the optimization of conventional and development of innovative vector-control tools.
Assessing the acoustic behaviour of Anopheles gambiae (s.l.) dsxF mutants: implications for vector control
14647M. P. Su, M. Georgiades, J. Bagi, K. Kyrou, A. Crisanti and J. T. Albert, Parasites and Vectors, 13:507. 2020-10-07 13:33:23.
We analysed sound emissions and acoustic preference in a doublesex mutant previously used to collapse Anopheles gambiae (s.l.) cages.
Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae
14015R. Carballar-Lejarazú, C. Ogaugwu, T. Tushar, A. Kelsey, T. B. Pham, J. Murphy, H. Schmidt, Y. Lee, G. C. Lanzaro and A. A. James, Proceedings of the National Academy of Sciences, 202010214. 2020-08-24 12:38:12.
We show here that the Cas9/guide RNA-based gene-drive components of a genetically-engineered malaria mosquito vector, Anopheles gambiae, achieve key target product profile requirements for efficacy and performance.
Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi
13593A. Adolfi, V. M. Gantz, N. Jasinskiene, H.-F. Lee, K. Hwang, E. A. Bulger, A. Ramaiah, J. B. Bennett, G. Terradas, J. J. Emerson, J. M. Marshall, E. Bier and A. A. James, bioRxiv, 2020.08.02.233056. 2020-08-02 12:59:26.
We developed the first recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and a functional resistant allele does not prevent drive invasion.
Detecting the population dynamics of an autosomal sex ratio distorter transgene in malaria vector mosquitoes
13607P. Pollegioni, A. R. North, T. Persampieri, A. Bucci, R. L. Minuz, D. A. Groneberg, T. Nolan, P. A. Papathanos, A. Crisanti and R. Muller, Journal of Applied Ecology, 11. 2020-06-18 12:44:16.
A sex-distorting autosomal transgene has been developed recently in G3 mosquitoes, a laboratory strain of the malaria vectorAnopheles gambiaes.l. Following the World Health Organization guidance framework for the testing of GM mosquitoes, we assessed the dynamics of this transgene in large cages using a joint experimental modelling approach. We performed a 4-month experiment in large, indoor cages to study the population genetics of the transgene.
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.
Mosquitoes engineered to resist the malaria parasite
12440Anonymous, Lab+Life Scientist, 2020-06-07 20:22:39.
Anopheles mosquitoes that have been genetically engineered with multiple antimalaria molecules, acting at different stages of the malaria life cycle, are strongly resistant to the parasite that causes malaria and are unlikely to lose that resistance quickly.
New study highlights success of gene drive technology with preventing mosquito-spread diseases
12401A. Meckler-Pacheco, The California Aggie, 2020-05-25 18:47:25.
For the past 30 years, researchers have studied the usage of gene drive technology to stop the spread of malaria. The idea is to create genetically engineered mosquitoes (GEM) that are either resistant to carrying the malaria parasite or that fail to reproduce, which would result in the reduction of the mosquito population. The gene drive technology relies on the use of the Cas-9 enzyme, which ensures the passing of the new modified genes onto offspring in the introduced population.
Hope rises as scientists eliminate malaria mosquitoes
11953A. Adeyemi, New Telegraph, 2020-05-14 17:57:14.
A team of researchers led by Imperial College London have spread a genetic modification that distorted the sex ratio through a population of caged Anopheles gambiae mosquitoes using ‘gene drive’ technology. According to the results of their study published yesterday in ‘Nature Biotechnology,’ the modification they initiated in the laboratory created more male offspring that was able to eliminate populations of malaria mosquitoes in the lab experiments.
Malaria mosquitoes eliminated in lab by creating all-male offsprings
11945Aishwarya, Inshorts, 2020-05-13 17:53:53.
Imperial College London-led team used 'gene drive' technology to spread genetic modification that distorted sex ratio through caged breed of malaria mosquitoes. This caused mosquitoes to produce more male offspring, eventually leading to no female birth. The study suggested such mosquitoes carrying a sex-distorter gene drive could help spread male bias within local malaria-carrying populations.
Researchers use “gene drive” technology to eliminate malaria mosquitoes in lab experiments
11619J. Ives, News Medical Life Sciences, 2020-05-13 16:15:18.
A team led by Imperial College London spread a genetic modification that distorts the sex ratio through a population of caged Anopheles gambiae mosquitoes using 'gene drive' technology.
Genetically-manipulated male mosquitoes could eliminate females
11617B. Coxworth, New Atlas, 2020-05-13 16:13:30.
Several years ago, we heard how scientists were looking at eradicating malaria-carrying mosquitoes by making the females infertile. Now they're going a step further, by eliminating the females altogether.
Researchers discover way to eliminate malaria carrying mosquitoes
11615S. Digon, International Business Times, 2020-05-13 16:12:04.
Researchers from the Imperial College London have come up with a genetic modification that will pave the way for the elimination of malaria mosquitoes. Scientists say that the alteration distorts the sex ratio of caged Anopheles gambiae mosquitoes using what they call a ‘gene drive’ technology.
Malaria mosquitoes eliminated in lab by creating all male populations
11609H. Dunning, Imperial College London, 2020-05-11 16:07:00.
A team led by Imperial College London spread a genetic modification that distorts the sex ratio through a population of caged Anopheles gambiae mosquitoes using ‘gene drive’ technology.
A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae
11463A. Simoni, A. M. Hammond, A. K. Beaghton, R. Galizi, C. Taxiarchi, K. Kyrou, D. Meacci, M. Gribble, G. Morselli, A. Burt, T. Nolan and A. Crisanti, Nature Biotechnology, 2020-05-11 15:15:55.
We report a male-biased sex-distorter gene drive (SDGD) in the human malaria vector Anopheles gambiae.
Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement
11465A. Hoermann, S. Tapanelli, P. Capriotti, E. K. G. Masters, T. Habtewold, G. K. Christophides and N. Windbichler, bioRxiv, 2020-05-10 15:19:12.
Here we explore how minimal genetic modifications of endogenous mosquito genes can convert them directly into non-autonomous gene drives without disrupting their expression.
Mosquito-Borne Diseases Emergence/Resurgence and How to Effectively Control It Biologically
12383H. Dahmana and O. Mediannikov, Pathogens, 9:26. 2020-04-23 17:49:22.
Deadly pathogens and parasites are transmitted by vectors and the mosquito is considered the most threatening vector in public health, transmitting these pathogens to humans and animals. We are currently witnessing the emergence/resurgence in new regions/populations of the most important mosquito-borne diseases, such as arboviruses and malaria. This resurgence may be the consequence of numerous complex parameters, but the major cause remains the mismanagement of insecticide use and the emergence of resistance. Biological control programmes have rendered promising results but several highly effective techniques, such as genetic manipulation, remain insufficiently considered as a control mechanism. Currently, new strategies based on attractive toxic sugar baits and new agents, such as Wolbachia and Asaia, are being intensively studied for potential use as alternatives to chemicals. Research into new insecticides, Insect Growth Regulators, and repellent compounds is pressing, and the improvement of biological strategies may provide key solutions to prevent outbreaks, decrease the danger to at-risk populations, and mitigate resistance.
Gene editing could fight malaria by causing only male mosquitos to be born
11958L. Dormehl, Digital Trends, 2020-04-14 18:01:16.
What’s the theoretically easiest way to ensure that a population of mosquitos is not able to sustain itself through breeding? Make sure that there aren’t enough females, of course. That’s the exploratory approach being pioneered by researchers at the U.K.’s Imperial College London, who have developed a way of distorting the sex ratio in species of Anopheles gambiae mosquitoes to ensure that offspring are predominantly male. Over a relatively short period of time, this causes the population of mosquitos to collapse — and, potentially, halts one of the main vectors for spreading diseases like malaria as a result.
Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes mosquitoes
14309H. Schmidt, T. C. Collier, M. J. Hanemaaijer, P. D. Houston, Y. Lee and G. C. Lanzaro, Nature Communications, 11. 2020-03-16 12:39:04.
ere we report the results of a survey of 1280 genomes of the mosquitoes Anopheles gambiae, An. coluzzii, and Aedes aegypti in which we determine that similar to 90% of all protein-encoding CGD target genes in natural populations include at least one target site with no DRAs at a frequency of >= 1.0%.
Transcontinental dispersal of Anopheles gambiae occurred from West African origin via serial founder events
14311H. Schmidt, Y. Lee, T. C. Collier, M. J. Hanemaaijer, O. D. Kirstein, A. Ouledi, M. Muleba, D. E. Norris, M. Slatkin, A. J. Cornel and G. C. Lanzaro, Communications Biology, 2. 2019-12-19 12:47:18.
Here we present population genomic analyses of 111 specimens sampled from west to east Africa, including the first whole genome sequences from oceanic islands, the Comoros.
Development of genetic control strategies for insect pests using CRISPR/Cas9 Développement de méthodes de lutte génétique contre de l’insecte nuisible basé sur le system CRISPR/Cas9
18505E. Green, Université de Strasbourg, 2019-12-17 14:20:21.
nsect pest control remains an important economic, environmental, and public health challenge. CRISPR/Cas9 gene drive (GD) is a novel genetic control strategy. GDs are genetic systems that can rapidly invade a population. This manuscript presents my efforts to develop gene drives in two important pest species, Anopheles gambiae, a major vector of malaria, and Drosophila suzukii, a global crop pest. The goals of this project were to develop a suppression gene drive in D. suzukii, to reduce population size, and a modification drive in An. gambiae, to reduce malaria transmission. While I was unable to produce a functional gene drive in D. suzukii, the efforts and protocols presented here can serve as a baseline for future work in this economically important crop pest. In An. gambiae, I successfully characterized two transgenic lines, one of which significantly blocks malaria transmission to a rodent model. Finally, I present my efforts to engineer a new modification gene drive strategy, indirect gene drive.
Community Engagement Prior to a Small-Scale Pilot of the Sterile Insect Technique in Kwazulu-Natal, South Africa 2018
25918P. N. Manana, J. Zikhali, D. Dlamini, S. Gumede, N. Mabaso, T. Mpungose and G. Munhenga, Journal of Public Health and Disease Prevention, 2. 2019-12-16 13:14:53.
Approximately 165 000 listeners were engaged during two 30 minute radio interviews at a local radio station. Two hundred and fifty farm workers, several outpatients from primary health care facilities and 1400 secondary school pupils were given education on malaria transmission and control strategies including SIT. Furthermore, two road shows; one in areas around Mamfene and a second at KwaPhuza market, were done. In total, 447 falciparum-specific rapid diagnostic tests were conducted with 20 people testing positive. These patients were immediately treated for malaria. Conclusions: The campaigns showed that the majority of community members are informed concerning malaria transmission and control. However, there is a lack of understanding regarding the SIT as a vector control option. A more extensive public awareness programme on SIT as a vector control strategy is recommended to prepare the community of Mamfene for future small field pilot sterile male mosquito releases.
A synthetic male-specific sterilization system using the mammalian pro-apoptotic factor in a malaria vector mosquito
16645D. S. Yamamoto, M. Sumitani, K. Kasashima, H. Sezutsu, H. Matsuoka and H. Kato, Scientific Reports, 9:11. 2019-06-03 19:52:01.
We produced a transgenic mosquito line that expresses mouse Bax under the control of this testis-specific promoter. Transgenic mosquito males exhibited aberrant testes without functional sperm and complete sterility, whereas transgenic females maintained normal fecundity. Despite their abnormal testes, the transgenic males maintained normal function of male accessory glands and typical mating behaviour. As a result of mating with these males, females showed refractoriness to further mating. These results suggest that transgenic males induce female sterility via mating. The mosquito is one of the most important disease vectors, and the control of their population benefits global public health.
MGDrivE: A modular simulation framework for the spread of gene drives through spatially-explicit mosquito populations
3941Sánchez C, HMW, Sean L.; Bennett, Jared B.; Marshall, John M., Methods in Ecology and Evolution, 10:1-24. 2019-01-19 00:00:00.
Malaria, dengue, Zika, and other mosquito-borne diseases continue to pose a major global health burden through much of the world, despite the widespread distribution of insecticide-based tools and antimalarial drugs. The advent of CRISPR/Cas9-based gene editing and its demonstrated ability to streamline the development of gene drive systems has reignited interest in the application of this technology to the control of mosquitoes and the diseases they transmit. The versatility of this technology has enabled a wide range of gene drive architectures to be realized, creating a need for their population-level and spatial dynamics to be explored. 2.We present MGDrivE (Mosquito Gene Drive Explorer): a simulation framework designed to investigate the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations. A key strength of the MGDrivE framework is its modularity: a) a genetic inheritance module accommodates the dynamics of gene drive systems displaying userdefined inheritance patterns, b) a population dynamic module accommodates the life history of a variety of mosquito disease vectors and insect agricultural pests, and c) a landscape module generates the metapopulation model by which insect populations are connected via migration over space. 3.Example MGDrivE simulations are presented to demonstrate the application of the framework to CRISPR/Cas9-based homing gene drive for: a) driving a disease-refractory gene into a population (i.e. population replacement), and b) disrupting a gene required for female fertility (i.e. population suppression), incorporating homing-resistant alleles in both cases. Further documentation and use examples are provided at the project's Github repository. 4.MGDrivE is an open-source R package freely available on CRAN. We intend the package to provide a flexible tool capable of modeling novel inheritance-modifying constructs as they are proposed and become available. The field of gene drive is moving very quickly, and we welcome suggestions for future development.
Sterile insect technique field trials to eliminate malaria under way
25913Anonymous, SA Department of Science and Innovation, 2018-10-29 13:06:00.
The first South African research trial for the biological control of mosquitoes using the sterile insect technique started in Jozini in KwaZulu-Natal earlier this month, with funding from the Department of Science and Technology. South Africa is making significant progress in reducing the incidence of malaria, and is now at a level where the country in a prime position to begin with complementary vector control strategies that address the problem of insecticide resistance. However, indoor residual spraying (IRS) using DDT and pyrethroid insecticides, while effective in controlling the disease, is unlikely to eliminate malaria on its own. IRS targets mainly indoor feeding and resting mosquitoes, and is not effective against vectors that feed and rest outdoors such as Anopheles arabiensis, which is a major contributor to outdoor transmission in South Africa's malaria-affected provinces. One of the supplementary methods being explored is the use of the sterile insect technique (SIT). This works like birth control to suppress mosquito populations and reduce the spread of malaria. The technique involves the mass-rearing and sterilisation of male mosquitoes before they are released in the wild.
Global report on insecticide resistance in malaria vectors: 2010-2016.
12683WHO, World Health Organization, 2018-05-01 18:13:11.
Insecticide-based vector control is a cornerstone in the fight against malaria. Selection of vector-control interventions should take into account the resistance status of local mosquito vectors along with other factors associated with intervention deployment and use such as availability, cost and cost -effectiveness as well as population acceptance or compliance. Strategic insecticide resistance monitoring is therefore essential to inform evidence-based vector control.
CRISPR/Cas9 -mediated gene knockout of Anopheles gambiae FREP1 suppresses malaria parasite infection
3973Dong, YS, Maria L.; Marois, Eric; Dimopoulos, George, PLOS Pathogens, 14:e1006898. 2018-01-11 00:00:00.
The causative agent of malaria, Plasmodium, has to complete a complex infection cycle in the Anopheles gambiae mosquito vector in order to reach the salivary gland from where it can be transmitted to a human host. The parasite’s development in the mosquito relies on numerous host factors (agonists), and their inhibition or inactivation can thereby result in suppression of infection and consequently malaria transmission. The recently developed CRISPR/Cas9-based genome editing tools for Anopheles mosquitoes provide new and promising opportunities to delete (inactivate) Plasmodium agonists to better understand their function and for blocking malaria transmission. Here we have established a modified CRISPR/Cas9 genome editing technique for malaria vector A. gambiae mosquitoes. Through this approach we have inactivated the fibrinogen-related protein 1 (FREP1) gene, via CRISPR/Cas9 genome editing, and the impact of this manipulation on the mosquito’s susceptibility to Plasmodium and on mosquito fitness. FREP1 knockout mutants showed a profound suppression of infection with both human and rodent malaria parasites, while it also resulted in fitness costs: a significantly lower blood-feeding propensity, fecundity and egg hatching rate, and a retarded larval development and pupation time, and reduced longevity after a blood meal.
Current vector control challenges in the fight against malaria
16269G. Benelli and J. C. Beier, Acta Tropica, 174:91-96. 2017-07-07 16:47:31.
The majority of National Malaria Control Programs in Africa still rely on indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs). These methods reduce malaria incidence but generally have little impact on malaria prevalence. In addition to outdoor transmission, growing levels of insecticide resistance in targeted vectors threaten the efficacy of LLINs and IRS.
Mating competitiveness of sterile genetic sexing strain males (GAMA) under laboratory and semi-field conditions: Steps towards the use of the Sterile Insect Technique to control the major malaria vector Anopheles arabiensis in South Africa
25911G. Munhenga, B. D. Brooke, J. R. L. Gilles, K. Slabbert, A. Kemp, L. C. Dandalo, O. R. Wood, L. N. Lobb, D. Govender, M. Renke and L. L. Koekemoer, Parasites and Vectors, 9:122. 2016-03-02 13:00:23.
Anopheles arabiensis Patton is primarily responsible for malaria transmission in South Africa after successful suppression of other major vector species using indoor spraying of residual insecticides. Control of An. arabiensis using current insecticide based approaches is proving difficult owing to the development of insecticide resistance, and variable feeding and resting behaviours. The use of the sterile insect technique as an area-wide integrated pest management system to supplement the control of An. arabiensis was proposed for South Africa and is currently under investigation. The success of this technique is dependent on the ability of laboratory-reared sterile males to compete with wild males for mates. As part of the research and development of the SIT technique for use against An. arabiensis in South Africa, radio-sensitivity and mating competitiveness of a local An. arabiensis sexing strain were assessed.
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.
The Impact of Pyrethroid Resistance on the Efficacy of Insecticide-Treated Bed Nets against African Anopheline Mosquitoes: Systematic Review and Meta-Analysis.
12678C. Strode, S. Donegan, P. Garner, A. A. Enayati and J. Hemingway, PLOS Medicine, 11:e1001619. 2014-03-18 17:48:58.
This meta-analysis found that ITNs are more effective than UTNs regardless of resistance. There appears to be a relationship between resistance and the RD for mosquito mortality in laboratory and field studies. However, the substantive heterogeneity in the studies' results and design may mask the true relationship between resistance and the RD, and the results need to be interpreted with caution. Our analysis suggests the potential for cumulative meta-analysis in entomological trials, but further field research in this area will require specialists in the field to work together to improve the quality of trials, and to standardise designs, assessment, and reporting of both resistance and entomological outcomes.
Swarming and mating behavior of male Anopheles arabiensis Patton (Diptera: Culicidae) in an area of the Sterile Insect Technique Project in Dongola, northern Sudan
25815M. M. Hassan, H. M. Zain, M. A. Basheer, H. E. F. Elhaj and B. B. El-Sayed, Acta Tropica, 132:S64-S69. 2013-11-27 08:57:21.
The problems facing the conventional mosquito control methods including resistance to insecticides have led to the development of alternative methods such as the Sterile Insect Technique (SIT) to suppress populations of the malaria vector Anopheles arabiensis in northern Sudan. This method entails the release of large numbers of irradiated males to compete against wild conspecifics for mating with virgin females in the field. The swarming and mating behaviors of this species were conducted at two field sites during the period 2009-2012 in Dongola, northern Sudan. Observations were made in the field sites and in a contained semi-field enclosure. In addition, participation of released irradiated-marked males in the swarms of wild mosquito was investigated. Swarms were observed on sunset in the vicinity of larval habitats around irrigation channel and stopped with the onset of the darkness about 21-25 min after the start. Swarms were observed above visual markers such as palm trees, bare ground, and manure. Several couples were observed leaving the swarms in copula in the direction of the sunlight. The majority of copulations were observed within 12-15 min of the start of swarming. Relatively low insemination rates (28%) of females collected from coupling pairs were observed. Irradiated-marked males were observed to join the natural swarms regularly, indicating their probable competitiveness with the other wild males. These findings enhance the feasibility of staging an SIT campaign against malaria vector in Northern State-Sudan. Copyright (C) International Atomic Energy Agency 2013. Published by Elsevier B.V. All rights reserved.
Modelling the spatial spread of a homing endonuclease gene in a mosquito population
4177North, AB, A.; Godfray, H. C. J., Journal of Applied Ecology, 50:1216-1225. 2013-01-15 00:00:00.
Homing endonuclease genes (HEGs) exist naturally in many single-celled organisms and can show extremely strong genetic drive allowing them to spread through populations into which they are introduced. They are being investigated as tools to manipulate the populations of important vectors of human disease, in particular the mosquitoes that transmit malaria. Before HEGs can be deployed, it is important to study their spatial spread in order to design efficient release strategies. A spatially explicit model is developed to study the spread of a HEG through a landscape whose structure is defined by the distribution of mosquito breeding and feeding sites. The model is motivated by the biology of the major vectors of malaria in Africa. The conditions for spread, fixation and loss of two major types of HEG are explored in different landscapes. In landscapes where mosquito resources are abundant, the conditions for spread are well approximated by a mean-field model. Where a HEG imposes a genetic load, it can cause population extinction, though spatial models more often predict population suppression. In certain types of landscapes where mosquito resources are rare, an introduced HEG may be prevented from moving between local mosquito populations and so a simple release strategy is unlikely to be effective, yet if the HEG succeeds in spreading population extinction is a feasible outcome. Increasing the number of release sites at the expense of releasing fewer mosquitoes per site reduces the probability that a HEG will fail.Synthesis and applications. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study.
Evaluating the potential of the sterile insect technique for malaria control: relative fitness and mating compatibility between laboratory colonized and a wild population of Anopheles arabiensis from the Kruger National Park, South Africa
25909G. Munhenga, B. D. Brooke, T. F. Chirwa, R. H. Hunt, M. Coetzee, D. Govender and L. L. Koekemoer, Parasites and Vectors, 4:208. 2011-10-31 12:48:58.
The successful suppression of a target insect population using the sterile insect technique (SIT) partly depends on the premise that the laboratory insects used for mass rearing are genetically compatible with the target population, that the mating competitiveness of laboratory reared males is at least comparable to that of their wild counterparts, and that mass rearing and sterilization processes do not in themselves compromise male fitness to a degree that precludes them from successfully competing for mates in the wild. This study investigated the fitness and sexual cross-compatibility between samples of field collected and laboratory reared An. arabiensis under laboratory conditions.
Pyrethroid resistance in African anopheline mosquitoes: what are the implications for malaria control?
12676H. Ranson, R. N’Guessan, J. Lines, N. Moiroux, Z. Nkuni and V. Corbel, Trends in Parasitology, 27:91-98. 2011-02-01 17:44:55.
The use of pyrethroid insecticides in malaria vector control has increased dramatically in the past decade through the scale up of insecticide treated net distribution programmes and indoor residual spraying campaigns. Inevitably, the major malaria vectors have developed resistance to these insecticides and the resistance alleles are spreading at an exceptionally rapid rate throughout Africa. Although substantial progress has been made on understanding the causes of pyrethroid resistance, remarkably few studies have focused on the epidemiological impact of resistance on current malaria control activities. As we move into the malaria eradication era, it is vital that the implications of insecticide resistance are understood and strategies to mitigate these effects are implemented.
Requirements for effective malaria control with homing endonuclease genes
4203Deredec, AG, H. C. J.; Burt, A., Proceedings of the National Academy of Sciences of the United States of America, 108:e874-e880. 2011-01-21 00:00:00.
Malaria continues to impose a substantial burden on human health. We have previously proposed that biological approaches to control the mosquito vector of disease could be developed using homing endonuclease genes (HEGs), a class of selfish or parasitic gene that exists naturally in many microbes. Recent lab studies have demonstrated that HEGs can function in mosquitoes. We constructed and analyzed a model of mosquito population genetics and malaria epidemiology to determine how well HEGs need to function in order to have a significant effect on the burden of disease. Our model, combined with currently available data, indicates that populations of Anopheles gambiae could be eliminated by releasing 2-3 HEGs targeting female fertility genes, or a driving-Y chromosome that is transmitted to 75-96% of progeny. Combinations of fertility-targeting HEGs and Y drive may also be effective. It is possible to eliminate the disease without eliminating the vector, but the parameter space producing this outcome appears to be small. HEGs causing a quantitative reduction in adult survival can be more effective than those targeting female fertility, but the selection coefficients that need to be imposed are still large, unless many HEGs are to be released. Simulations show that HEG-based strategies can be effective over socially relevant time frames. Important limiting assumptions of the models are that there is only a single vector species, and we model a homogeneous population, not a landscape. Nevertheless, we conclude that HEG-based approaches could have a transformational effect on malaria control efforts.
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.
Field site selection: getting it right first time around
25817C. A. Malcolm, B. El Sayed, A. Babiker, R. Girod, D. Fontenille, B. G. J. Knols, A. H. Nugud and M. Q. Benedict, Malaria Journal, 8. 2009-11-16 09:57:52.
The selection of suitable field sites for integrated control of Anopheles mosquitoes using the sterile insect technique (SIT) requires consideration of the full gamut of factors facing most proposed control strategies, but four criteria identify an ideal site: 1) a single malaria vector, 2) an unstructured, relatively low density target population, 3) isolation of the target population and 4) actual or potential malaria incidence. Such a site can exist in a diverse range of situations or can be created. Two contrasting SIT field sites are examined here: the desert-flanked Dongola Reach of the Nile River in Northern State, Sudan, where malaria is endemic, and the island of La Reunion, where autochthonous malaria is rare but risk is persistent. The single malaria-transmitting vector at both sites is Anopheles arabiensis. In Sudan, the target area is a narrow 500 km corridor stretching from the rocky terrain at the Fourth Cataract - just above the new Merowe Dam, to the northernmost edge of the species range, close to Egypt. Vector distribution and temporal changes in density depend on the Nile level, ambient temperature and human activities. On La Reunion, the An. arabiensis population is coastal, limited and divided into three areas by altitude and exposure to the trade winds on the east coast. Mosquito vectors for other diseases are an issue at both sites, but of primary importance on La Reunion due to the recent chikungunya epidemic. The similarities and differences between these two sites in terms of suitability are discussed in the context of area-wide integrated vector management incorporating the SIT.
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.
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.
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.
First Anopheles arabiensis germline transformation: Toward the development of a transgenic genetic sexing strain
16649H. C. Bossin, J. Thailayil, F. Catteruccia, J. P. Benton, A. Crisanti, M. Q. Benedict, B. G. Knols and A. S. Robinson, American Journal of Tropical Medicine and Hygiene, 75:66-66. 2006-11-01 20:17:39.
The ability to genetically engineer mosquitoes is likely to have major implications for the development and implementation of genetic control systems against mosquito disease vectors such as the Sterile Insect Technique (SIT). In particular, genetically transformed mosquito strains can be created for genetic marking and sexing, two key factors known to influence the effectiveness of SIT programmes. In addition, the removal of biting females before releasing sterile males in the field will be of critical importance as they contribute to disease transmission and reduce the efficiency of the release campaign. Parallel to the creation of a conventional genetic sexing strain (Y-translocation of a resistance marker), our group is undertaking a transgenic approach to the development of an A. arabiensis genetic sexing strain (GSS). The sex separation strategy under investigation relies on the sex-specific properties of the A. gambiae B2tubulin gene regulatory regions. It is hoped this approach will achieve the high sex separation efficiency (above 99%) and strain stability required for safe and efficient male-only SIT releases. We report here the successful development of transgenic A. arabiensis lines using the pPB[DsRed]B2EGFP construct. Wild-type A. arabiensis embryos were injected with a mixture of pPB[DsRed]B2EGFP and helper plasmid phsppBac (700 and 300 ng/µI respectively) following an appropriate protocol. Injections generated several transgenic sexing lines. The effectiveness of the transgenic-based sex-separation procedure, the stability of transgenic mosquito GSS under various (mass-)rearing regimes, as well as the viability and reproductive competitiveness of transgenic sterile males are being assessed.
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.
Radiation-induced sterility for pupal and adult stages of the malaria mosquito Anopheles arabiensis
25750M. E. H. Helinski, A. G. Parker and B. G. J. Knols, Malaria Journal, 5:10. 2006-05-16 15:23:31.
The optimal dose for male insects to be released in an SIT programme depends on their level of sterility and competitiveness. The use of semi-sterilizing doses to produce more competitive insects is discussed. The most convenient developmental stage for mosquito irradiation on a mass-scale are pupae, but pupal irradiation resulted in a lower insemination rate at the highest dose compared to adult irradiation. On the basis of this study, a suitable dose range that includes semi-sterilizing doses is identified to initiate competitiveness experiments for males irradiated at both developmental stages.
Stable transformation of the yellow fever mosquito, Aedes aegypti, with the Hermes element from the housefly
6254N. Jasinskiene, C. J. Coates, M. Q. Benedict, A. J. Cornel, C. S. Rafferty, A. A. James and F. H. Collins, Proceedings of the National Academy of Sciences of the United States of America, 95:3743-3747. 1998-03-07 19:28:29.
The mosquito Aedes aegypti is the world's most important vector of yellow fever and dengue viruses, Work is currently in progress to control the transmission of these viruses by genetically altering the capacity of wild Ae, aegypti populations to support virus replication. The germ-line transformation system reported here constitutes a major advance toward the implementation of this control strategy, A modified Hermes transposon carrying a 4.7-kb fragment of genomic DNA that includes a wild-type allele of the Drosophila melanogaster cinnabar (cn) gene was used to transform a white-eyed recipient strain of Ae, aegypti. Microinfection of preblastoderm mosquito embryos with this construct resulted in 50% of the emergent G(0) adults showing some color in their eyes, Three transformed families were recovered, each resulting from an independent insertion event of the cn(+)-carrying transposon, The cn(+) gene functioned as a semidominant transgene and segregated in Mendelian ratios, Hermes shows great promise as a vector for efficient, heritable, and stable transformation of this important mosquito vector species.
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