Keywords: Population suppression
CRISPR-Cas9 suppression gene drives for Nile tilapia control: prospects in sub-Saharan African freshwater ecosystems
35509Bobo, E. D., All Life, 19. 2026-03-16 15:14:01.
CRISPR-based suppression gene drives represent a promising tool for managing invasive Nile tilapia (Oreochromis niloticus) populations in sub-Saharan Africa’s freshwater ecosystems. Introduced through aquaculture, Nile tilapia supports livelihoods but also causes severe biodiversity loss. This review explores the technical feasibility of CRISPR-Cas9 suppression gene drives, specifically homing and Driving-Y drive systems, as species-specific, potentially self-sustaining biocontrol strategies. The theoretical effectiveness of these gene drive systems in reducing invasive Nile tilapia and restoring ecological balance is discussed within a precautionary framework. This study addresses the urgent need to protect native tilapia species, which are listed as Critically Endangered, Endangered, and Vulnerable by the IUCN. Gene drives have the potential to reduce invasive populations and restore ecological balance. However, their effectiveness can be compromised by extensive hybridization with native Oreochromis species and resistance evolution in genetically diverse populations. Therefore, the ecological, ethical, and socioeconomic risks of gene drive systems were examined in the context of the Convention on Biological Diversity and Cartagena Protocol. Hence, integrating molecular innovations with strong policy frameworks, stakeholder engagement, and comprehensive risk assessment is essential. CRISPR-Cas9 suppression drives deployment requires careful evaluation across ecological, ethical, and governance contexts to safeguard native ichthyofauna.
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.
Spatial Dynamics and Sterilization Range of Incompatible Aedes albopictus Males: Advancing Toward an Optimized IIT Approach
35474Lampazzi, E., Virgillito, C., Caputo, B., et al., Tropical Medicine and Infectious Disease, 11. 2026-02-06 18:17:05.
The Incompatible Insect Technique (IIT) is a species-specific, eco-friendly mosquito control method that relies on releasing Wolbachia-infected males, which induce cytoplasmic incompatibility (CI), rendering eggs inviable when mating with wild females. Aiming at optimizing IIT protocols in terms of cost-effectiveness, data on incompatible male dispersal and survival and the distance- and time-related impact of induced sterility are fundamental. This study plans to fill this gap and reports findings from a two-year field trial (2022–2023) at the ENEA-Casaccia Research Center, based on single-spot releases of incompatible Aedes albopictus males (ARwP strain). Male releases were carried out in late September 2022 (~15,000 released males) and the early Ae. albopictus season (at the end of June 2023; ~24,000 released males). Fifty-eight ovitraps were located at a 20–900 m distance from the ARwP release spot and were monitored weekly from May to November to assess egg hatching rates and measure CI effects in relation to both distance and time. Following the 2023 release, samples of adults were collected at increasing distances from the release site and at multiple post-release time points to assess, individually, wild female fertility and ARwP male dispersal and survival using Wolbachia as a genetic marker. Statistical analyses revealed that: (a) the highest reduction in the egg hatching was found within 100 m from the release spot (46.5% and 19.9%, respectively, in 2022 and 2023) but remained significant even at greater distances (29.9% and 7.7% at 300 m, respectively, in 2022 and 2023); (b) accordingly, the highest reduction in the wild female fertility occurred within 100 m from the release spot (47.3%), but similar effects were recognizable up to 600 m; (c) the overflooding ratio of the ARwP males did not significantly differ between 3 and 11 days after the release, with ARwP males remaining active up to 18 days and dispersing as far as 400 m. These results demonstrate the potential of localized, non-inundative IIT trials to furnish clues for the setup of spatially optimized release strategies, especially in scaled-up applications. The study also emphasizes the need for standardized assessment tools and further research regarding environmental and behavioral factors influencing long-term suppression outcomes.
Assessing target genes for homing suppression gene drive
35447Xu, X., Fang, J., Chen, J. et al., The EMBO Journal, 2026-02-06 17:52:26.
Gene drives are engineered alleles that bias their own inheritance in offspring, enabling the spread of specific traits throughout a population. Targeting female fertility genes in a gene drive can be an efficient strategy for population suppression. In this study, we investigated nine female fertility genes in Drosophila melanogaster using CRISPR-based homing gene drives. Employing a multiplexed gRNA approach to prevent the formation of functional resistance alleles, we aimed to maintain high drive-conversion efficiency with low fitness costs in female drive-carriers. Drive efficiency was assessed in individual crosses and had varied performance across different target genes. Notably, drives targeting the octopamine β2 receptor (oct) and stall (stl) genes exhibited the highest drive-conversion rates and were further tested in cages. A drive targeting stl successfully suppressed a cage population with a high release frequency, though suppression failed in another replicate cage with a lower initial release frequency. Fitness costs in female drive carriers were observed in test cages, impacting the overall efficiency of population suppression. Further tests on the fertility of these lines using individual crosses indicated that some fitness costs were due to maternal deposition of Cas9 combined with new gRNA expression, which would only occur in progeny of drive males when testing split drives with separate Cas9 (when mimicking cages with complete drives) but not for complete drive systems. This could enable success in complete drives with higher maternal Cas9 deposition, even if cage experiments in split drives fail. Overall, our findings identify oct and stl as promising fertility targets and demonstrate both the potential and the constraints of fertility-based suppression drives, providing empirical evidence to guide the design and assessment of more efficient population control strategies.
Field implementation of the sterile insect technique against Aedes aegypti in Recife, Brazil: operational challenges and impact of release frequency on vector dynamics
35418Macedo, A.T., Carvalho, D.O., Gomez, M. et al., Infectious Diseases of Poverty, 15. 2026-02-02 16:59:43.
The sterile insect technique (SIT) is an environmentally friendly tool for suppressing Aedes aegypti populations. While promising in controlled settings, its application in large urban environments presents logistical and biological challenges. This trial focused on releasing sterile males, sent from a long-distance production facility to suppress the local mosquito population. Sterile males of Ae. aegypti were mass-reared, irradiated, and transported 712.2 km from a central facility to Recife, Brazil. Releases were performed once (SIT 1 ×) or twice per week (SIT 2 ×). Entomological indices—including eggs/trap per day (ETD), hatch rate, induced sterility, and adult female abundance—were monitored through ovitraps and BG-Sentinel traps. Data were analyzed using generalized linear mixed models (GLMMs) and Bayesian time-series modeling (CausalImpact). Dose–response experiments established that pupae required 35 Gy and adults 65 Gy to achieve > 99% sterility, with no difference between gamma and X-ray sources. Adult sterilization was effective across 24–96 h post-emergence, facilitating operational flexibility. Handling and transport reduced flight ability by up to 35 percentage points, highlighting cumulative stress effects. In field trials, SIT 1 × yielded limited suppression, with ETD values remaining similar to or higher than those of the control. In contrast, SIT 2 × produced consistent suppression, reducing ETD by 39%, hatch rate by 33%, and female abundance by 51%. In this study, increasing the release frequency was essential to achieve significant model outcomes, representing varying degrees of mild suppression of Ae. aegypti in a complex urban setting. In Addition, male handling, chilling, and transport emphasize the need to reduce the exposure to these parameters by improving the protocols. These results highlight key areas for scaling SIT within integrated vector management strategies in tropical urban settings.
Research Advances and Challenges of Gene Drive Technology in Mosquito-Borne Disease Control
35363Yun Jiaqi, Ma Qin, Wang Guandong, et al., Laboratory Animal and Comparative Medicine, 45:773-783. 2026-01-14 12:01:39.
Mosquito-borne diseases (such as malaria, dengue fever, Zika virus disease, and Chikungunya) pose major threats to global public health, while traditional control methods based on chemical pesticides face severe challenges including enhanced drug resistance in vector mosquitoes and environmental pollution. Genetic control strategies have become high-potential alternative solutions for mosquito control due to their species specificity and environmental friendliness. Gene drive technology uses gene editing tools such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) to enable specific genes to efficiently spread in target mosquito populations through "super-Mendelian inheritance", offering a revolutionary strategy for the prevention and control of mosquito-borne diseases. This review systematically summarizes key advances, core challenges, and response strategies of gene drive technology in this field. Research advances: (1) In Anopheles malaria vectors, population suppression drives targeting sex determination genes or female reproductive genes can cause female sterility or skewed sex ratios to achieve population suppression. Population replacement gene drive strategies targeting host genes associated with Plasmodium infection or delivering anti-Plasmodium effector molecules in Anopheles can effectively block pathogen transmission. (2) In Aedes mosquito vectors of arboviruses, targeting female flight-essential genes achieves population suppression, and coupling of antiviral effector systems with drive elements is explored. Optimized split gene drive strategies demonstrate high cutting and recombination efficiency, and models predict safe and controllable spread of disease-resistance traits. (3) In Culex mosquitoes transmitting lymphatic filariasis, homology drive elements are integrated into two genes involved in the eye pigment synthesis pathway, allowing clear visualization of gene drive efficiency through eye color. Core Challenges: technological challenges include low homologous recombination repair efficiency, non-homologous end joining repair causing resistance allele generation, CRISPR/Cas9 off-target effects, and species adaptation differences. Ecological and safety challenges involve gene pool pollution caused by accidental spread of drive elements, potential ecological balance impacts, and long-term irreversible risks. Response strategies and prospects: employing multiplex guide RNA (gRNA) targeting strategies to enhance drive stability and combat potential resistance. Developing reversible designs such as synthetic resistance, reversal drives, and immunizing reversal drives as "genetic brakes". Establishing long-term ecological monitoring systems and mathematical modeling for risk assessment. Exploring "environmentally responsive drives" to enhance controllability. Future research should continuously optimize drive efficiency and specificity, deepen ecological risk evaluation, strengthen international cooperation, and promote ethical consensus and regulatory framework construction, with the aim of making gene drive technology a sustainable prevention and control strategy to address the global health challenge of mosquito-borne diseases under the premise of safety and controllability.
Rethinking the future of mosquito control
35341Kabirul Bashar, Dr Zonaed Siddiki. Dr Zonaed Siddiki, et al., Dhaka Tribune, 2025-12-17 11:37:26.
Bangladesh is once again in the grip of a severe dengue and chikungunya crisis in 2025. Hospitals are overwhelmed, fever wards are full, and doctors are working tirelessly. Families live in fear of mosquito bites, while daily news reports chronicle rising infections and deaths. As of December 16, 2025, the Directorate General of Health Services (DGHS) has reported more than 100,000 confirmed dengue cases and 409 deaths. However, this figure represents only the tip of the iceberg, as it reflects data solely from hospitalized patients, specifically from 77 hospitals in Dhaka and reports from 64 civil surgeon offices. A substantial number of dengue patients are receiving treatment at home or in various small and large hospitals and clinics that are not included in the official count. This underscores the overwhelming pressure on the country’s health system. At the same time, the Institute of Epidemiology, Disease Control and Research (IEDCR) has recorded a resurgence of chikungunya, reporting 337 suspected cases, 153 of which were laboratory-confirmed in Dhaka between January and May 2025. Researchers estimate that the true number of chikungunya infections this year may be close to one hundred thousand. As chikungunya testing is available only in a limited number of major hospitals in Dhaka, many cases remain undiagnosed and unreported.
Homing gene drive strains for genetic suppression of agricultural insect pests
35331Yadav, Amarish K.; Tarrand, Ariel E.; Scott, Maxwell J., Entomologia Generalis, 45:1577 - 1590. 2025-12-04 14:52:03.
Agricultural insect pests cause substantial losses in crop productivity each year. Genetic-based strategies provide economical and environmentally friendly ways to limit pests that reproduce sexually. In contrast to conventional genetic methods (e.g. SIT), homing gene drives (HGDs) are potentially capable of suppressing or modifying an entire pest population in a short period of time after releasing a small number of HGD insects. The advent of CRISPR/Cas gene editing tools has simplified the engineering of gene drives, and the progress made on HGDs in various insects in the recent past is encouraging. However, to date HGDs have been developed and evaluated in only a few agricultural pest species. These drives have been designed to suppress populations by targeting genes essential for female development or fertility. Homing gene drive relies on homology directed repair (HDR) of the Cas9-mediated double-stranded DNA break in germ cells. Consequently, the use of other DNA repair pathways such as non-homologous end joining (NHEJ) and micro-homology mediated end joining (MMEJ) can retard homing. Further, establishment of functional resistant alleles through these end-joining pathways is one of the major challenges associated with HGDs. Development of HGDs in some pest species is challenging due to the technical difficulties of making transgenics. Identification and characterization of germline-specific promoters and other regulatory elements to achieve precise HDR (in early meiosis) can facilitate efficient homing. In this review, we highlight the recent progress made towards developing HGDs in agricultural insect pests with insights gained from studies in model organisms (e.g. Drosophila melanogaster).
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.
Dispersal and survival of gamma-irradiated Culex quinquefasciatus: Implications for sterile insect technique applications
35207Nungki Hapsari Suryaningtyas, Raden Wisnu Nurcahyo, Beni Ernawan, et al., Open Veterinary Journal, 15:3054-3062. 2025-10-02 14:51:05.
Culex quinquefasciatus is a major vector of filariasis and other mosquito-borne diseases. The sterile insect technique (SIT) has been widely used to suppress mosquito populations, but its effectiveness depends on the dispersal, survival, and competitiveness of sterile males. This study evaluated the dispersal range, survival rate, and recapture success of gamma-irradiated Cx. quinquefasciatus under field conditions. A mark-release-recapture (MRR) experiment was conducted using sterile male and female Cx. quinquefasciatus. Two release events were conducted, and recapture data were collected over seven days using BG-Sentinel-2 traps baited with octanol placed within a 250-m radius. The irradiated males traveled an average of 143.18 m (FR50: 92.78 m; FR90: 220.02 m), and the females dispersed 146.26 m (FR50: 95.26 m; FR90: 227.25 m). Dispersal distance was significantly influenced by release site in males (p = 0.0089) and females (p = 0.0042) but not by recapture day (p > 0.89). Recapture location significantly affected dispersal in both sexes (p < 0.0001). The daily survival probabilities of males and females were 0.88 and 0.69, respectively, with corresponding life expectancies of 7.57 and 2.71 days. The dispersal and survival of sterile Cx. quinquefasciatus are affected by release strategies. To optimize SIT, further studies should refine the marking techniques, explore a combination of trapping methods, and evaluate the dispersal patterns across varied landscapes. These findings offer valuable insights into improving the implementation of SIT for Cx. quinquefasciatus population control.
The role of the transformer gene in sex determination and its employment in CRISPR/Cas9-based homing gene drive in the global fruit pest Drosophila suzukii
35185Dan Deng, Xueying Yi, Wen Wen, Liuqing He, Wei Peng, Insect Biochemistry and Molecular Biology, 184. 2025-09-29 08:45:13.
Sex determination of Diptera is established by the cascade genes such as transformer (tra), though the primary signals for sex determination differ among different insects. Here, we report the isolation, expression and function of tra gene in an invasive pest, Drosophila suzukii, and study the potential use of the D. suzukii tra (Dstra) gene in CRISPR/Cas9-based homing gene drive for genetic-based pest management. The Dstra gene is highly conserved in structure and has a sex-specific transcript. To test the function of this gene in sex determination, Dstra dsRNA was injected into embryos. Almost all XX embryos developed into masculinized phenotypic male adults with intersex morphology. Abnormal ovaries were revealed in XX pseudomales upon dissection. Based on the necessary role of Dstra for female development, we developed and evaluated a homing gene drive that targets Dstra in D. suzukii. The drive component consisting of multiplex Dstra single guide RNAs and Cas9 with Dsvasa promoter was introduced into the Dstra locus. Abnormal development of both the external genitalia and gonads was observed in G0 and G1 chromosomal female adults that expressed the male-specific doublesex (dsx) transcript. Interestingly, knocking out Dstra led to significantly reduced fertility in adults of corresponding sex and moderate transmission rates of the DsRed gene (63.54 %) were observed. Our results not only confirm the conserved function of the Dstra gene in sex determination, but also highlight the potential of sex conversion-based suppression gene-drive strategy targeting the Dstra gene in controlling of D. suzukii populations.
Leveraging Sex Determination Systems for Genetic Biocontrol of Dipteran Pests
35178Maxwell J. Scott, Zhijian Tu, Current Opinion in Insect Science, 2025-09-26 14:24:25.
Genetic biocontrol is an increasingly important way to suppress insect pest populations and to mitigate their economic and health impact. One key advantage is that it is species-specific as it relies on mating of released males with wild females to either suppress or modify populations. The latter is through rendering females incompetent at disease transmission. Sex separation is critical to ensure the efficiency of these control programs, and it is essential in the case of vector control to avoid releasing females that can transmit pathogens. Modern genetic methods provide the opportunity to target or manipulate components of the sex determination systems to facilitate genetic biocontrol with new means to effectively accomplish sex-specific selection, lethality, or sterility. For example, sex-specific splicing elements in genes in the sex determination pathway are used to produce sex-specific markers. Sex-linked recessive lethal alleles are used to differentially eliminate the transgene-marked sex chromosome from males to produce non-transgenic males. Knocking out or knocking down sex-specific isoforms of genes in the sex determination pathway is employed to confer female-specific lethality or sterility. Sex determination pathways and sex chromosomes are also targeted for gene drives that suppress pest populations by introducing extreme sex ratio biases. Here we review these and other recent advances on the genetic technologies for pest control that have benefited from knowledge of sex determination systems in Diptera.
Suppression of Aedes albopictus in Sri Lanka using the Sterile Insect Technique (SIT) with a sustained effect
35157Menaka Hapugoda, Nilmini Silva Gunawardene, Tharaka Ranathunge, Sudath Samaraweera, K. Karunathilake, Bazoumana B.D. Sow, Gayan Parakrama Withanage, Indika Weerasinghe, Hamidou Maiga and Jeremy Bouyer, Parasite, 32. 2025-09-22 10:50:08.
Dengue fever remains a significant public health concern in Sri Lanka, leading to recurrent epidemics and imposing substantial socio-economic burdens. This study aimed to assess the efficacy of the Sterile Insect Technique (SIT) against Aedes albopictus (Skuse), the predominant dengue vector in the country, through a pilot field trial of an Integrated Vector Management (IVM) strategy including the SIT. The pilot trial was conducted in the Gampaha district, which reports the second-highest number of dengue cases in the country. A total of 3,300,000 sterile males, exposed to a 50 Gy radiation dose, were released over 33 weeks (100,000/week) within a 30-hectare release area. Entomological assessments were conducted at 115 trapping stations over a period of 71 weeks (October 2020–August 2022). Induced sterility of 98.16% in mosquito eggs was reached within the release area as compared to the control area (binomial generalized linear mixed model, deviance 2.408, df = 2, p = 0.016), indicating a notable impact of the SIT. The trial achieved nearly 98% suppression of adult vector mosquitoes, with a sustained suppression effect for 13 weeks post cessation of releases. These findings suggest that SIT can be effectively integrated as a potential additional tool into the future IVM strategy in Sri Lanka.
Reprogramming Sex for Vector Control: Maleness-Associated Transgenes in Aedes albopictus
35151Doron Shalom Yishai Zaada, Philippos Aris Papathanos, Eric Marois, Current Opinion in Insect Science, 2025-09-22 10:21:15.
Among other challenges, the world currently faces the expansion of pest insects such as the tiger mosquito Aedes albopictus, a growing threat to public health due to the pathogens it can transmit. Current control approaches based on insecticides or elimination of mosquito larval breeding sites are insufficient to suppress this highly invasive species. The discovery of Nix, a gene necessary and sufficient to determine the male sex in this mosquito, opens new prospects for genetic control strategies, in particular those based on transgenes that convert females into males, or that reduce female fitness. Such forms of genetic control could be effective on larger spatial and time scales compared to classical control approaches. This overview of current and emerging genetic control strategies targeting Aedes mosquitoes emphasizes the unique characteristics of Ae. albopictus, that make it particularly amenable to masculinization-based genetic control.
Experimental demonstration of daisy chain gene drive and modelling of daisy suppression systems
35147Jialiang Guo, Weizhe Chen, Jackson Champer, bioRxiv, 2025-09-22 10:06:58.
CRISPR-based gene drive can address ecological problems by biased inheritance coupled with an effector for either population modification of suppression. However, the potential risk of uncontrolled spread impedes some applications of gene drive. Daisy chain gene drives have received much attention as a potential approach to overcome this problem. They potentially allow the efficient spread of drive elements in a target population, but are ultimately self-limiting. This is achieved by splitting a normal gene drive system into multiple dependent drive elements, where each element can bias the inheritance of another, except one non-driving element. With the successive loss of each chain link, the spread of transgenic elements will slow down and eventually stop. Here, we use modelling to assess the population dynamics of daisy chain drives in both panmictic and continuous space models, focusing on suppression systems. We find that achieving population elimination through a single release of daisy chain gene drives is possible but difficult, with relatively high requirements for drive performance and release size. These effects are substantially amplified in spatial models. We also constructed two configurations of daisy chain gene drives in Drosophila melanogaster as a proof-of-principle. One is a rescue drive for population modification, and the other aims for population suppression by targeting a haplosufficient female fertility gene. These drives all functioned within expectations at moderate efficiency in individual crosses. However, the drive design failed to spread in cage populations because of higher than expected fitness costs. Overall, our study demonstrates that daisy chain systems may be promising candidates for both modification and suppression, but challenges remain in both construction and potential deployment in large regions.
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.
Integrated vector management with the sterile insect technique component for the suppression of Aedes aegypti in an urban setting in Indonesia
34954Sasmita HI, Neoh K-B, Ernawan B, Indarwatmi M, Nasution IA, Fitrianto N, et al., PLoS Neglected Tropical Diseases, 2025-07-08 13:14:26.
The sterile insect technique (SIT) involves subjecting laboratory-bred male mosquitoes to radiation, typically gamma rays, X-rays, or electrons, that render them sterile. These sterile male mosquitoes are then released into the field to mate with wild female mosquitoes. From that mating, no viable eggs are produced. The SIT is a mosquito population control strategy that prevents the spread of the dengue virus through Aedes aegypti female mosquitoes. Considerable progress has been made regarding the SIT, and its effectiveness has been tested in numerous regions for managing local mosquito populations. In the present study, the field performance of sterile male mosquitoes was evaluated through a mark–release–recapture study, which was followed by an SIT trial. In an SIT pilot trial, pre-release control measures, including insecticide application and mosquito breeding site removal, were applied within the framework of integrated vector management. Community engagement activities were designed to ensure community acceptance and support for the SIT. The trial led to substantial reductions in the egg hatching, numbers of eggs and female mosquitoes despite challenges related to sterile male production and population isolation. This study revealed the key factors contributing to the success of an SIT trial to be the field performance of sterile male mosquitoes, complementary vector control methods, population isolation, and support from local residents.
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.
Mosquito Miracle: Breakthrough Brings Hope for Bangladesh in Dengue Fight
34837Staff Correspondent, Digi Bangla Tech, 2025-05-10 19:42:52.
A major scientific breakthrough is offering new hope for Bangladesh in its battle against dengue. An international team of researchers has successfully developed a strain of Aedes aegypti mosquitoes infected with Wolbachia bacteria, which are capable of adapting to the local environment of Dhaka city. Dubbed as “good mosquitoes,” this innovation opens a new, safe, and biological pathway for controlling the spread of dengue and other mosquito-borne arboviral diseases in the country, according to the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). The research team includes scientists from QIMR Berghofer Medical Research Institute in Australia, the University of Queensland, icddr,b, and the United States Centers for Disease Control and Prevention. The findings were recently published in the journal Nature’s Scientific Reports. According to icddr,b, dengue has emerged as a severe public health threat in Bangladesh. In 2023 alone, a record 321,000 people were infected, with more than 1,700 deaths—making it the deadliest year on record. Rapid urbanization, erratic rainfall, and rising temperatures have contributed to the spread of Aedes mosquitoes, the primary vector of dengue. Simultaneously, the effectiveness of conventional insecticide-based mosquito control methods is declining due to growing resistance among mosquito populations. This has prompted scientists worldwide to seek more sustainable solutions, with the use of "good mosquitoes" being one of the most promising. Researchers explained that Wolbachia was chosen because it prevents Aedes mosquitoes from transmitting dengue, chikungunya, and Zika viruses, without harming humans or the environment. Wolbachia is a naturally occurring bacterium found in butterflies, fruit flies, and some mosquito species, though not in Aedes aegypti. This bacterium cannot infect humans or animals, nor is it transmissible through bites or contact.
Stronger population suppression by gene drive targeting doublesex from dominant female-sterile resistance alleles
34799Weizhe Chen, Ziye Wang, Jackson Champer, bioRxiv, 2025-04-23 11:00:18.
CRISPR homing drives can be used to suppress a population by targeting female fertility genes. They convert wild-type alleles to drive alleles in the germline of drive heterozygotes by homology-directed repair after DNA cleavage. However, resistance alleles produced by end-joining pose a great threat to homing drive. They prevent further recognition by Cas9, and therefore weaken suppressive power, or even stop suppression if they preserve the function of the target gene. We used multiplexed gRNAs targeting doublesex in Drosophila to avoid functional resistance and create resistance alleles that were dominant female-sterile. This occurred because the male dsx transcript was generated in females by disruption of the female-specific splicing acceptor site. We rescued dominant sterility of the drive by providing an alternate splicing site. As desired, the drive was recessive female sterile and yielded high drive inheritance among the progeny of both male and female drive heterozygotes. The dominant-sterile resistance alleles enabled stronger suppression in computational models, even in the face of modest drive efficiency and fitness costs. However, we found that male drive homozygotes were also sterile because they used the rescue splice site. Attempts to rescue males with alternate expression arrangements were not successful, though some male homozygotes had less severe intersex phenotypes. Though this negatively impacted the drive, models showed that it still had significantly improved suppressive power. Therefore, this design may have wide applicability to dsx-based suppression gene drives in a variety of organisms with intermediate homing drive performance.
Anticipating evolutionary responses of mosquito mating systems to population suppression with mass-reared males
34745Bonsall, M.B., Cator, L.J., Current Opinion in Insect Science, 68. 2025-04-06 19:52:32.
Strategies that rely on the mass release of males to suppress mosquito populations will exert selective pressure on natural mating systems. Here, we investigate how mass releases might affect the mating behaviors of wild target populations. We highlight gaps in our understanding of both variation in these aspects of mosquito behavior and the evolutionary forces that maintain variation within and between populations. We provide a mathematical framework for integrating mosquito mating ecology into models of population suppression. Given that these strategies are being increasingly deployed, anticipating and managing evolutionary responses of target population behavior should be a priority for research.
Global asymptotic stability in a delay stage structured model for mosquito population suppression
34720Huang, Mg., Yu, Js., Applied Mathematics, 40:112-136. 2025-03-31 14:42:25.
A promising avenue to control mosquito-borne diseases such as dengue, malaria, and Zika involves releasing male mosquitoes carrying the bacterium Wolbachia in wild areas to drive female sterility by a mechanism called cytoplasmic incompatibility (CI). In this work, we initiate a preliminary assessment of how the combined impact of dispersal, incomplete CI and mating competitiveness on mosquito population suppression by a delay differential equation model. Our theoretical analyses indicate that the immigration of eggs plays a significant role in the suppression dynamics. For the case without egg immigration, we identify a threshold dispersal rate v* of adult mosquitoes, threshold CI density ξ*, and threshold release ratio r*. A successful mosquito suppression would be established only when v < v*, ξ > ξ*, and r(t) ≥ r* uniformly. The immigration of eggs causes the threshold dynamics to be invalid, and warns an absolute failure of population suppression. The monotonicity of the adult steady-state in the dispersal rate and CI intensity indicates that choosing a suitable Wolbachia strain with strong CI intensity, or bringing down the dispersal rate of mosquitoes by blocking the suppression zones is a feasible strategy to obtain a better suppression level.
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.
Mark-Release-Recapture of Packed and Shipped Aedes aegypti with Wolbachia: Implications for Conducting Remote Incompatible Insect Technique Programs
34640Ohm, J. R., Lynd, A., McGowan, A., et al., The American Journal of Tropical Medicine and Hygiene, 2025-03-21 14:44:30.
Male mosquitoes containing the endosymbiont Wolbachia (Wb+) can be used as a tool to suppress wild mosquito populations through a technique termed incompatible insect technique (IIT). IIT programs reduce wild mosquitoes via incompatible matings between released males and wild females to reduce the number of viable offspring produced in the next generation. Successful programs rely on regular release of incompatible males to outcompete wild males for female mates. Past IIT programs have relied on local production of Wb+ males to support regular releases of incompatible males. Here, we evaluated the survival and dispersal of packed and shipped Wb+ Aedes aegypti males in mark-release-recapture studies at a release site in the British Virgin Islands (BVI), separated by over 3,600 miles from the centralized production facility. Released mosquitoes were recaptured using BG-Sentinel 2 traps collected daily for up to 7 days after release. Wb+ male mosquitoes packed and shipped from a centralized production facility performed similarly to males that were locally reared in the BVI in survival, dispersal, and recapture rates. Our results support the conclusion that packing and shipping live Wb+ male mosquitoes does not impact their ability to survive and disperse in release sites and suggests that IIT mosquito control programs can feasibly be conducted nearly anywhere in the world without the need for local mosquito production facilities.
Engineering drive–selection balance for localized population suppression with neutral dynamics
34597Willis, K., and Burt, A., Proceedings of the National Academy of Sciences, 122. 2025-03-18 10:29:28.
While the release of sterile males has been highly successful in suppressing some pest populations, it is impractical for many species due to the males disappearing after a single generation, necessitating large, repeated releases to maintain sufficient impact. Synthetic gene drives promise more efficient approaches since they can increase in frequency from rare, yet this also allows them to spread across a landscape, which may not always be desired. Between these two extremes are selectively neutral genetic constructs which persist at the frequency they are released, offering the potential for efficient suppression that remains localized. One way to achieve this would be to have perfect balance, at all construct frequencies, between gene drive increasing frequency and selection decreasing it. Here, we describe a way to closely approximate this balance using a toxin–antidote genetic construct that causes recessive lethality or sterility, encodes a genomic editor that makes dominant lethal or sterile edits in the genome, and provides protection against the action or consequences of the editing. Computer modeling shows that this design can be 100-fold more efficient than sterile males, increasing to 1,000-fold when released alongside a genetic booster. We describe designs for CRISPR-based molecular construction, including options that avoid using recoded genes as antidotes.
A comparative assessment of self-limiting genetic control strategies for population suppression
34572Yue Han, Jackson Champer, Molecular Biology and Evolution, 2025-03-12 16:21:17.
Genetic control strategies are promising solutions for control of pest populations and invasive species. Methods utilizing repeated releases of males such as Sterile Insect Technique (SIT), Release of Insects carrying a Dominant Lethal (RIDL), self-limiting gene drives, and gene disruptors are highly controllable methods, ensuring biosafety. Although models of these strategies have been built, detailed comparisons are lacking, particularly for some of the newer strategies. Here, we conducted a thorough comparative assessment of self-limiting genetic control strategies by individual-based simulation models. Specifically, we find that repeated releases greatly enhance suppression power of weak and self-limiting gene drives, enabling population elimination with even low efficiency and high fitness costs. Moreover, dominant female sterility further strengthens self-limiting systems that can either use gene drive or disruptors that target genes without a mechanism to bias their own inheritance. Some of these strategies are highly persistent, resulting in relatively low release ratios even when released males suffer high fitness costs. To quantitively evaluate different strategies independent from ecological impact, we proposed constant-population genetic load, which achieves over 95% accuracy in predicting simulation outcomes for most strategies, though it is not as precise in a few frequency-dependent systems. Our results suggest that many new self-limiting strategies are safe, flexible, and more cost-effective than traditional SIT and RIDL, and thus have great potential for population suppression of insects and other pests.
Making sex deadly for insects could control pests that carry disease and harm crops
34559Bill Sullivan, The Conversation, 2025-03-04 17:08:29.
Insects do a lot more harm than ruining picnics. Some insects spread devastating diseases, while others cause staggering economic losses in agriculture. To control some of these pests, scientists are developing males that make sex a deadly event. The stakes are high. Mosquitoes carry viruses such as dengue, West Nile and Zika, as well as parasites that cause malaria. Researchers estimate that mosquitoes have caused the deaths of 52 billion people overall – nearly half of all the humans that have ever lived. Other insects cause major crop damage, jeopardizing the food supply and driving up prices. According to the Food and Agriculture Organization of the United Nations, 20% to 40% of global crop production is lost to pests annually at a cost of US$70 billion. Pesticides have been the front-line defense against insects, but many bugs have evolved resistance to these chemicals. Some pesticides can indiscriminately kill beneficial insects, harm the environment and endanger human and animal health. Some researchers worry that certain pesticides can cause cancer or have damaging effects on human nervous and endocrine systems. I’m a microbiology researcher studying infectious disease. New solutions that do not harm humans and the environment to control disease-carrying insects and agricultural pests could lead to fewer people contracting dangerous diseases. In the past few years, a variety of genetic engineering approaches have emerged as promising tactics to combat problematic insects.
Wolbachia-based mosquito control: Environmental perspectives on population suppression and replacement strategies
34543Bhattacharyya, J., Roelke, D.L., Acta Tropica, 262. 2025-02-25 10:59:30.
Mosquito-borne diseases pose a significant threat to global health, and traditional mosquito control methods often fall short of effectiveness. A promising alternative is the biological control strategy of transinfecting mosquitoes with Wolbachia, a bacterium capable of outcompeting harmful pathogens and reducing the ability of mosquitoes to transmit diseases. However, Wolbachia infections are sensitive to abiotic environmental factors such as temperature and humidity, which can affect their densities in mosquitoes and, consequently, their ability to block pathogens. This review evaluates the effectiveness of different Wolbachia strains transinfected into mosquitoes in reducing mosquito-borne diseases. It explores how Wolbachia contributes to mosquito population control and pathogen interference, highlighting the importance of mathematical models in understanding Wolbachia transmission dynamics. Additionally, the review addresses the potential impact on arboviral transmission and the challenges posed by environmental fluctuations in mosquito control programs.
Gene drive-based population suppression in the malaria vector Anopheles stephensi
34372Xu, X., Chen, J., Wang, Y. et al., Nature Communications, 16:1007. 2025-01-28 14:41:08.
Gene drives are alleles that can bias the inheritance of specific traits in target populations for the purpose of modification or suppression. Here, we construct a homing suppression drive in the major urban malaria vector Anopheles stephensi targeting the female-specific exon of doublesex, incorporating two gRNAs and a nanos-Cas9 to reduce functional resistance and improve female heterozygote fitness. Our results show that the drive was recessive sterile in both females and males, with various intersex phenotypes in drive homozygotes. Both male and female drive heterozygotes show only moderate drive conversion, indicating that the nanos promoter has lower activity in A. stephensi than in Anopheles gambiae. By amplicon sequencing, we detect a very low level of resistance allele formation. Combination of the homing suppression drive and a vasa-Cas9 line boosts the drive conversion rate of the homing drive to 100%, suggesting the use of similar systems for population suppression in a continuous release strategy with a lower release rate than SIT or fsRIDL techniques. This study contributes valuable insights to the development of more efficient and environmentally friendly pest control tools aimed at disrupting disease transmission.
Gene Drive Technology Offers Hope For Malaria Vector Control
34365Evrim Ağacı, The Pinnacle Gazette, 2025-01-28 13:46:11.
A team of scientists has developed an innovative gene drive targeting Anopheles stephensi mosquitoes, a key malaria vector in urban areas. Their strategy uses CRISPR technology to disrupt the doublesex (dsx) gene, crucial for female fertility, thereby reducing mosquito populations. The gene drive, called HSDdsx, showed promising results in suppressing mosquito reproduction with minimal resistance, indicating long-term effectiveness. This approach could help control malaria transmission and reduce reliance on pesticides. The research also opens doors for future advancements in pest control, with potential applications against other disease vectors, marking a significant step toward environmentally friendly solutions.
Genetically Engineered Male Insects Shorten Their Mates’ Lifespans
34253Sneha Khedkar, The Scientist, 2025-01-13 15:13:56.
On a still night, as the air is thick with silence, the sharp, whining buzz of a mosquito shatters the calm. These blood-sucking insects that disturb people’s deep slumber are also responsible for spreading diseases such as dengue, chikungunya, malaria and Zika fever, which affect millions of people each year worldwide. Given the harmful effects of pesticides on the environment, combined with the emergence of mosquitoes resistant to pesticides, scientists are looking for alternative environment-friendly approaches for pest management. Now, researchers have developed a new population control method where male insects carrying toxic proteins can poison disease-spreading females during mating. The results, published in Nature Communications, describe a genetic biocontrol method that offers a fast and effective solution to managing pests. Such approaches are not entirely new. In the 1950s, when researchers mated female insects with radiologically sterilized males, they did not produce offsprings, reducing the next generation’s population. More recently, scientists propagated transgenes in insects that lower the fitness of future generations, resulting in decreased insect population. Although such methods are promising, they require at least one generation to take effect: Female insects may not produce offsprings, but they can continue transmitting infections. “As we’ve learned from COVID-19, reducing the spread of these diseases as quickly as possible is important to prevent epidemics,” said study author Samuel Beach, a graduate student in biologist Maciej Maselko’s lab at Macquarie University, in a press release.
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.
Wolbachia-based mosquito control: Environmental perspectives on population suppression and replacement strategies
34213Joydeb Bhattacharyya, Daniel L. Roelke, Acta Tropica, 262. 2025-01-07 09:07:50.
Mosquito-borne diseases pose a significant threat to global health, and traditional mosquito control methods often fall short of effectiveness. A promising alternative is the biological control strategy of transinfecting mosquitoes with Wolbachia, a bacterium capable of outcompeting harmful pathogens and reducing the ability of mosquitoes to transmit diseases. However, Wolbachia infections are sensitive to abiotic environmental factors such as temperature and humidity, which can affect their densities in mosquitoes and, consequently, their ability to block pathogens. This review evaluates the effectiveness of different Wolbachia strains transinfected into mosquitoes in reducing mosquito-borne diseases. It explores how Wolbachia contributes to mosquito population control and pathogen interference, highlighting the importance of mathematical models in understanding Wolbachia transmission dynamics. Additionally, the review addresses the potential impact on arboviral transmission and the challenges posed by environmental fluctuations in mosquito control programs.
Engineering Resilient Gene Drives Towards Sustainable Malaria Control: Predicting, Testing and Overcoming Target Site Resistance
33379Ioanna Morianou, Lee Phillimore, Bhavin S. Khatri,, bioRxiv, 2024-11-04 13:56:24.
CRISPR-based gene drives are selfish genetic elements with the potential to spread through entire insect populations for sustainable vector control. Gene drives designed to disrupt the reproductive capacity of females can suppress laboratory populations of the malaria mosquito. However, any suppressive intervention will inevitably exert an evolutionary pressure for resistance. Here, we present a pipeline for the accelerated discovery, engineering, and testing of both natural and drive-induced variants that could reverse gene drive spread. We applied our method to stress-test a highly effective gene drive that has evaded resistance in all laboratory-contained releases to date, known as Ag(QFS)1. We showed that previously undetected resistant alleles can arise at low frequency, and discovered novel, partially resistant alleles that can perturb drive-invasion dynamics. We then engineered next-generation gene drives that can actively remove resistant alleles by targeting several highly conserved and non-overlapping sites in the female-specific exon of the doublesex gene. Our models predict that such gene drive designs could suppress large, natural populations of the malaria mosquito in the field.
Loss-of-function in testis-specific serine/threonine protein kinase triggers male infertility in an invasive moth
32506Wei, Z., Wang, Y., Zheng, K. et al., Communications Biology, 7. 2024-10-08 09:10:05.
Genetic biocontrol technologies present promising and eco-friendly strategies for the management of pest and insect-transmitted diseases. Although considerable advancements achieve in gene drive applications targeting mosquitoes, endeavors to combat agricultural pests have been somewhat restricted. Here, we identify that the testis-specific serine/threonine kinases (TSSKs) family is uniquely expressed in the testes of Cydia pomonella, a prominent global invasive species. We further generated male moths with disrupted the expression of TSSKs and those with TSSKs disrupted using RNA interference and CRISPR/Cas9 genetic editing techniques, resulting in significant disruptions in spermiogenesis, decreased sperm motility, and hindered development of eggs. Further explorations into the underlying post-transcriptional regulatory mechanisms reveales the involvement of lnc117962 as a competing endogenous RNA (ceRNA) for miR-3960, thereby regulating TSSKs. Notably, orchard trials demonstrates that the release of male strains can effectively suppress population growth. Our findings indicate that targeting TSSKs could serve as a feasible avenue for managing C. pomonella populations, offering significant insights and potential strategies for controlling invasive pests through genetic sterile insect technique (gSIT) technology.
Deployment of tethered gene drive for confined suppression in continuous space requires avoiding drive wave interference
31622Ruobing Feng, Jackson Champer, Molecular Ecology, 33. 2024-09-16 21:13:35.
Gene drives have great potential for suppression of pest populations and removal of exotic invasive species. CRISPR homing suppression drive is a powerful but unconfined drive, posing risks of uncontrolled spread. Thus, developing methods for confining a gene drive is of great significance. Tethered drive combines a confined system such as Toxin-Antidote Recessive Embryo drive with a strong drive such as a homing suppression drive. It can prevent the homing drive from spreading beyond the confined drive and can be constructed readily, giving it good prospects for future development. However, we have found that care must be taken when deploying tethered drive systems in some scenarios. Simulations of tethered drive in a panmictic population model reveal that successful deployment requires a proper release ratio between the two components, tailored to prevent the suppression drive from eliminating the confined system before it has the chance to spread. Spatial models where the population moves over a one-dimensional landscape display a more serious phenomenon of drive wave interference between the two tethered drive components. If the faster suppression drive wave catches up to the confined drive wave, success is still possible, but it is dependent on drive performance and ecological parameters. Two-dimensional simulations further restrict the parameter range for drive success. Thus, careful consideration must be given to drive performance and ecological conditions, as well as specific release proposals for potential application of tethered drive systems.
Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila
34760Chen, W., Guo, J., Liu, Y. et al., Nature Communications, 15. 2024-09-14 09:17:45.
CRISPR homing gene drives can suppress pest populations by targeting female fertility genes, converting wild-type alleles into drive alleles in the germline of drive heterozygotes. fsRIDL (female-specific Release of Insects carrying a Dominant Lethal) is a self-limiting population suppression strategy involving continual release of transgenic males carrying female lethal alleles. Here, we propose an improved pest suppression system called “Release of Insects carrying a Dominant-sterile Drive” (RIDD), combining performance characteristics of homing drive and fsRIDL. We construct a split RIDD system in Drosophila melanogaster by creating a 3-gRNA drive disrupting the doublesex female exon. Drive alleles bias their inheritance in males, while drive alleles and resistance alleles formed by end-joining cause dominant female sterility. Weekly releases of RIDD males progressively suppressed and eventually eliminated cage populations. Modeling shows that RIDD is substantially stronger than SIT and fsRIDL. RIDD is also self-limiting, potentially allowing targeted population suppression.
Population dynamics in spatial suppression gene drive models and the effect of resistance, density dependence, and life history
31190Xinyue Zhang, Weitang Sun, Isabel K. Kim, Philipp W. Messer, Jackson Champer, bioRxiv, 2024-08-27 08:13:04.
Due to their super-Mendelian inheritance, gene drive systems have the potential to provide revolutionary solutions to critical public health and environmental problems. For suppression drives, however, spatial structure can cause “chasing” population dynamics that may postpone target population elimination or even cause the drive to fail. In chasing, wild-type individuals elude the drive and recolonize previously suppressed areas. The drive can re-enter these recolonized areas, but often is not able to catch up to wild-type and finally eliminate it. Previous methods for chasing detection are only suitable to limited parameter ranges. In this study with expanded parameter ranges, we found that the shift from chasing dynamics to static equilibrium outcomes is continuous as drive performance is reduced. To quantify this, we defined a Weighted Average Nearest Neighbor statistic to assess the clustering degree during chasing, while also characterizing chasing by the per-generation chance of population elimination and drive loss. To detect chasing dynamics in local areas and to detect the start of chasing, we implemented Density-Based Spatial Clustering of Applications with Noise. Using these techniques, we determined the effect of arena size, resistance allele formation rate in both the germline and in the early embryo from maternally deposited Cas9, life history and reproduction strategies, and density-dependent growth curve shape on chasing outcomes. We found that larger real-world areas will be much more vulnerable to chasing and that species with overlapping generations, fecundity-based density dependence, and concave density-dependent growth curves have smaller and more clustered local chasing with a greater chance of eventual population elimination. We also found that embryo resistance and germline resistance hinder drive performance in different ways. These considerations will be important for determining the necessary drive performance parameters needed for success in different species, and whether future drives could potentially be considered as release candidates.
Non-Mendelian transmission of X chromosomes: mechanisms and impact on sex ratios and population dynamics in different breeding systems
31181Sally Adams; Andre Pires-daSilva, Biochemical Society Transactions, 2024-08-25 20:35:26.
The non-Mendelian transmission of sex chromosomes during gametogenesis carries significant implications, influencing sex ratios and shaping evolutionary dynamics. Here we focus on known mechanisms that drive non-Mendelian inheritance of X chromosomes during spermatogenesis and their impact on population dynamics in species with different breeding systems. In Drosophila and mice, X-linked drivers targeting Y-bearing sperm for elimination or limiting their fitness, tend to confer unfavourable effects, prompting the evolution of suppressors to mitigate their impact. This leads to a complex ongoing evolutionary arms race to maintain an equal balance of males and females. However, in certain insects and nematodes with XX/X0 sex determination, the preferential production of X-bearing sperm through atypical meiosis yields wild-type populations with highly skewed sex ratios, suggesting non-Mendelian transmission of the X may offer selective advantages in these species. Indeed, models suggest X-meiotic drivers could bolster population size and persistence under certain conditions, challenging the conventional view of their detrimental effects. Furthering our understanding of the diverse mechanisms and evolutionary consequences of non-Mendelian transmission of X chromosomes will provide insights into genetic inheritance, sex determination, and population dynamics, with implications for fundamental research and practical applications.
Wolbachia symbionts control sex in a parasitoid wasp using a horizontally acquired gene
29885Li C, Li CQ, Chen ZB, Liu BQ, Sun X, Wei KH, Li CY, Luan JB., Current Biology, 2024-05-07 15:55:59.
Host reproduction can be manipulated by bacterial symbionts in various ways. Parthenogenesis induction is the most effective type of reproduction manipulation by symbionts for their transmission. Insect sex is determined by regulation of doublesex (dsx) splicing through transformer2 (tra2) and transformer (tra) interaction. Although parthenogenesis induction by symbionts has been studied since the 1970s, its underlying molecular mechanism is unknown. Here we identify a Wolbachia parthenogenesis-induction feminization factor gene (piff) that targets sex-determining genes and causes female-producing parthenogenesis in the haplodiploid parasitoid Encarsia formosa. We found that Wolbachia elimination repressed expression of female-specific dsx and enhanced expression of male-specific dsx, which led to the production of wasp haploid male offspring. Furthermore, we found that E. formosa tra is truncated and non-functional, and Wolbachia has a functional tra homolog, termed piff, with an insect origin. Wolbachia PIFF can colocalize and interact with wasp TRA2. Moreover, Wolbachia piff has coordinated expression with tra2 and dsx of E. formosa. Our results demonstrate the bacterial symbiont Wolbachia has acquired an insect gene to manipulate the host sex determination cascade and induce parthenogenesis in wasps. This study reveals insect-to-bacteria horizontal gene transfer drives the evolution of animal sex determination systems, elucidating a striking mechanism of insect-microbe symbiosis.
Wolbachia Infection through Hybridization to Enhance an Incompatible Insect Technique-Based Suppression of Aedes albopictus in Eastern Spain
29086Cholvi M, Trelis M, Bueno-Marí R, Khoubbane M, Gil R, Marcilla A, Moretti R., Insects, 15. 2024-04-04 09:29:30.
Wolbachia bacteria occur naturally as symbionts of many insect species and are responsible for various phenomena that modify the hosts’ reproductive biology. Among them, cytoplasmic incompatibility (CI) refers to the sterility of eggs produced by crosses between infected males and females that are uninfected or infected by a non-compatible strain of these bacteria. CI can be exploited for vector control by establishing an opportune Wolbachia infection in a laboratory population of a target insect species and then releasing the infected males into the environment as sterilizing agents. In the present work, a suitable Wolbachia strain was introduced into a Spanish population of the Asian tiger mosquito, Aedes albopictus, through hybridization with the laboratory line, ARwP, already tested as an efficient control tool against this vector. The obtained hybrids were compared with the ARwP to ascertain the effects derived from transferring the infection to a different Ae. albopictus population. No significant differences between lines were found regarding survival, female fecundity, and egg fertility. Importantly, the eggs produced by crosses between males of the hybrid lines and unmodified wild females were 99.9% sterile. This result encourages further studies to explore the feasibility of a Wolbachia-based control program against the Asian tiger mosquito in Spain.
Effectiveness evaluation of mosquito suppression strategies on dengue transmission under changing temperature and precipitation
28984Kaihui Liu, Shuanghui Fang, Qiong Li, et al., Acta Tropica, 2024-03-05 20:16:41.
The haplolethal gene wupA of Drosophila exhibits potential as a target for an X-poisoning gene drive
28845Clancy D. Lawler, Ana Karla Parra Nuñez, Natalia Hernandes, Soumitra Bhide, Isabelle Lohrey, Simon Baxter, Charles Robin, bioRxiv, 2024-01-28 12:54:44.
A synthetic gene drive that targets haplolethal genes on the X-chromosome can skew the sex ratio towards males. Like an ‘X-shredder’ it does not involve ‘homing’ and that has advantages including the reduction of gene drive resistance allele formation. We examine this ‘X-poisoning’ strategy by targeting four of the 11 known X-linked haplolethal/haplosterile genes of Drosophila melanogaster with CRISPR/Cas9. We find that targeting the wupA gene during spermatogenesis skews the sex ratio so fewer than 14% of progeny are daughters. That is unless we cross the mutagenic males to X^XY female flies that bear attached-X chromosomes, which reverses the inheritance of the poisoned X chromosome so that sons inherit it from their father; in which case only 2% of the progeny are sons. These sex ratio biases suggests that most of the CRISPR/Cas9 mutants we induced in the wupA gene are haplolethal but some are recessive lethal. The males generating wupA mutants do not suffer from reduced fertility rather the haplolethal mutants arrest development in the late stages of embryogenesis well after fertilized eggs have been laid. This provides a distinct advantage over genetic manipulation strategies involving sterility which can be countered by the remating of females. We also find that wupA mutants that destroy the nuclear localization signal of shorter isoforms are not haplolethal as long as the open reading frame remains intact. Like D. melanogaster wupA orthologs of D. suzukii and Anopheles mosquitos are found on X chromosomes making wupA a viable X-poisoning target in multiple species.
Gene drive and genetic sex conversion in the global agricultural pest Ceratitis capitata
28802Meccariello, A., Hou, S., Davydova, S. et al., Nature Communications, 15:372. 2024-01-15 17:13:20.
Homing-based gene drives are recently proposed interventions promising the area-wide, species-specific genetic control of harmful insect populations. Here we characterise a first set of gene drives in a tephritid agricultural pest species, the Mediterranean fruit fly Ceratitis capitata (medfly). Our results show that the medfly is highly amenable to homing-based gene drive strategies. By targeting the medfly transformer gene, we also demonstrate how CRISPR-Cas9 gene drive can be coupled to sex conversion, whereby genetic females are transformed into fertile and harmless XX males. Given this unique malleability of sex determination, we modelled gene drive interventions that couple sex conversion and female sterility and found that such approaches could be effective and tolerant of resistant allele selection in the target population. Our results open the door for developing gene drive strains for the population suppression of the medfly and related tephritid pests by co-targeting female reproduction and shifting the reproductive sex ratio towards males. They demonstrate the untapped potential for gene drives to tackle agricultural pests in an environmentally friendly and economical way.
Population suppression with dominant female-lethal alleles is boosted by homing gene drive
28685Jinyu Zhu, Jingheng Chen, Yiran Liu, Xuejiao Xu, Jackson Champer, bioRxiv, 2023-12-07 10:24:25.
Methods to suppress pest insect populations using genetic constructs and repeated releases of male homozygotes have recently been shown to be an attractive alternative to older sterile insect technique based on radiation. Female-specific lethal alleles have substantially increased power, but still require large, sustained transgenic insect releases. Gene drive alleles bias their own inheritance to spread throughout populations, potentially allowing population suppression with a single, small-size release. However, suppression drives often suffer from efficiency issues, and the most well-studied type, homing drives, tend to spread without limit. In this study, we show that coupling female-specific lethal alleles with homing gene drive allowed substantial improvement in efficiency while still retaining the self-limiting nature (and thus confinement) of a lethal allele strategy. Using a mosquito model, we show the required releases sizes for population elimination in a variety of scenarios, including different density growth curves, with comparisons to other systems. Resistance alleles reduced the power of this method, but these could be overcome by targeting an essential gene with the drive while also providing rescue. A proof-of-principle demonstration of this system in Drosophila melanogaster was effective in both basing its inheritance and achieving high lethality among females that inherit the construct in the absence of antibiotic. Overall, our study shows that substantial improvements can be achieved in female-specific lethal systems for population suppression by combining them with a gene drive.
Measuring Host Fitness Effects and Transmission of Wolbachia Strains in Aedes aegypti Mosquitoes
28587Ross, P.A., Methods in Molecular Biology, 2739. 2023-11-29 15:49:58.
Lines of Aedes aegypti mosquitoes infected with heritable Wolbachia bacteria are being developed and released for arbovirus control. Coordinated releases of lab-reared Wolbachia mosquitoes have reduced local disease incidence by spreading virus-blocking Wolbachia strains and by crashing mosquito populations through incompatible male releases. The phenotypic effects of Wolbachia are diverse and depend on both genetics and the environment. Accurate assessments of Wolbachia effects in mosquitoes are essential, as such effects can make the difference between success and failure of a Wolbachia release program. This chapter provides guidelines for testing key Wolbachia host effects and transmission in Aedes aegypti: the most important arbovirus vector and the most common target of Wolbachia release programs. The protocols should be useful for evaluating mosquito strains prior to field release.
Symbiotic Wolbachia in mosquitoes and its role in reducing the transmission of mosquito-borne diseases: updates and prospects
28311A. Minwuyelet, G. P. Petronio, D. Yewhalaw, A. Sciarretta, I. Magnifico, D. Nicolosi, R. Di Marco and G. Atenafu, Frontiers in Microbiology, 14. 2023-11-08 08:20:47.
Mosquito-borne diseases such as malaria, dengue fever, West Nile virus, chikungunya, Zika fever, and filariasis have the greatest health and economic impact. These mosquito-borne diseases are a major cause of morbidity and mortality in tropical and sub-tropical areas. Due to the lack of effective vector containment strategies, the prevalence and severity of these diseases are increasing in endemic regions. Nowadays, mosquito infection by the endosymbiotic Wolbachia represents a promising new bio-control strategy. Wild-infected mosquitoes had been developing cytoplasmic incompatibility (CI), phenotypic alterations, and nutrition competition with pathogens. These reduce adult vector lifespan, interfere with reproduction, inhibit other pathogen growth in the vector, and increase insecticide susceptibility of the vector. Wild, uninfected mosquitoes can also establish stable infections through trans-infection and have the advantage of adaptability through pathogen defense, thereby selectively infecting uninfected mosquitoes and spreading to the entire population. This review aimed to evaluate the role of the Wolbachia symbiont with the mosquitoes (Aedes, Anopheles, and Culex) in reducing mosquito-borne diseases. Global databases such as PubMed, Web of Sciences, Scopus, and pro-Quest were accessed to search for potentially relevant articles. We used keywords: Wolbachia, Anopheles, Aedes, Culex, and mosquito were used alone or in combination during the literature search. Data were extracted from 56 articles’ texts, figures, and tables of the included article.
Unleashing a New Weapon on the Mosquito: A Mosquito
27987S. Nolen and E. Lutz, New York Times, 2023-09-29 08:05:43.
Five decades ago, entomologists confronting the many kinds of suffering that mosquitoes inflict on humans began to consider a new idea: What if, instead of killing the mosquitoes (a losing proposition in most places), you could disarm them? Even if you couldn’t keep them from biting people, what if you could block them from passing on disease? What if, in fact, you could use one infectious microbe to stop another? These scientists began to consider a parasitic bacteria called Wolbachia, which lives quietly in all kinds of insect species. A female mosquito with Wolbachia passes it on in her eggs to all of her offspring, who eventually pass it on to the next generation. But Wolbachia isn’t naturally found in the mosquito species that cause humans the most problems — the Aedes aegypti, the virus carrier, and the Anopheles subspecies, which carry malaria. If it were, it might eventually render those species essentially harmless. So how do you infect a mosquito with Wolbachia?
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.
Gene drives for invasive wasp control: Extinction is unlikely, with suppression dependent on dispersal and growth rates
27669P. J. Lester, D. O'Sullivan and G. L. W. Perry, Ecological Applications, 2023-08-24 06:36:30.
Abstract Gene drives offer a potentially revolutionary method for pest control over large spatial extents. These genetic modifications spread deleterious variants through a population and have been proposed as methods for pest suppression or even eradication. We examined the influence of local dispersal, long-distance and/or human-mediated dispersal, and variation in population growth, on the success of a gene drive for the control of invasive social wasps (Vespula vulgaris). Our simulations incorporated a spatially realistic environment containing variable habitat quality in New Zealand. Pest eradication was not observed, except in extreme and unrealistic scenarios of constant, widespread, and spatially intense releases of genetically modified individuals every year for decades. Instead, the regional persistence of genetically modified and wild-type wasps was predicted. Simulations using spatially homogeneous versus realistic landscapes (incorporating uninhabitable areas and dispersal barriers) showed little difference in overall population dynamics. Overall, little impact on wasp abundance was observed in the first 15?years post-introduction. After 25?years, populations were suppressed to levels <95% of starting populations. Populations exhibited ?chase dynamics? with population cycles in space, with local extinction occurring in some areas while wasps became abundant in others. Increasing the wasps' local dispersal distance increased the spatial and temporal variability of the occupied area and population suppression. Varying levels of human-associated long-distance dispersal had little effect on population dynamics. Increasing intrinsic population growth rates interacted with local dispersal to cause higher mean populations and substantially higher levels of variation in population suppression and the total amount of landscape occupied. Gene drives appear unlikely to cause a rapid and widespread extinction of this and probably other pests, but could offer long-term and cost-effective methods of pest suppression. The predicted level of <95% pest suppression would substantially reduce the predation pressure and competitive interactions of this invasive wasp on native species. However, the predicted long-term persistence of genetically modified pests will influence the ethics and likelihood of using gene drives for pest control, especially given concerns that modified wasps would eventually be transported back to their home range.
Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila
26903C. Weizhe, G. Jialiang, L. Yiran and C. Jackson, bioRxiv, 2023.07.17.549342. 2023-07-17 11:00:13.
Gene drive alleles, which bias their own inheritance and increase in frequency, show great promise for blocking disease transmission or directly suppressing pest populations. The most common engineered drive system is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of drive heterozygotes by homology-directed repair after CRISPR cleavage. One successful homing drive example targets a female-specific exon in doublesex in Anopheles mosquitos, suppressing the population by inducing recessive sterility in female drive homozygotes. We found that in Drosophila melanogaster, a 3-gRNA drive disrupting the doublesex female exon resulted in a masculine phenotype and dominant female sterility. Resistance alleles formed by end-joining repair were also dominant sterile. This was likely caused by expression of male-specific transcripts in females with drive and resistance alleles, disrupting sex development. Based on this construct, we proposed a new pest suppression system called Release of Insects carrying a Dominant-sterile Drive (RIDD). This entails continuously releasing drive heterozygous males, with drive and resistance alleles causing sterility in females. The drive remains at high frequency longer than currently used dominant female-lethal alleles (RIDL) due to drive conversion in males, and drive alleles also cause sterility based on resistance, both substantial advantages. With weekly releases of drive males into a cage population with overlapping generations, our RIDD system targeting dsx reached 100% prevalence within 27 weeks, progressively reducing egg production and eventually causing total population collapse. RIDD combines the merits of homing gene drive and RIDL. It is powerful but self-limiting, unlike unconfined standard homing drives, allowing for targeted population suppression.Competing Interest StatementThe authors have declared no competing interest.
Modeling the Impact of Migration on Mosquito Population Suppression
27422M. Huang and J. Yu, Qualitative Theory of Dynamical Systems, 22:134. 2023-07-17 08:45:23.
The Wolbachia-induced incompatible insect technique is a promising strategy for controlling wild mosquito populations. However, recent experimental studies have shown that mosquito migration into target areas dilutes the strategy’s effectiveness. In this work, we formulate a delay differential equation model to assess the impact of migration on mosquito population suppression. We identify that mosquito migration into an idealized target area makes it impossible to eliminate the target population completely. Our analysis identifies a lower bound of the suppression rate $$gamma ^*$$for a given migration number, which reveals the possible maximum reduction of wild population size in the peak season. For a given suppression rate target $$gamma _0>gamma ^*$$, we identify the permitted maximum migration number $$D(gamma _0)$$, above which is impossible to reduce the field mosquito density up to $$(1-gamma _0)times 100%$$in peak season. To reduce more than $$95%$$of Aedes albopictus population during its peak season in Guangzhou within six weeks, the required minimum release number of Wolbachia-infected males climbs steeply as the migration number increases to D(0.05).
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?
The cellular lives of Wolbachia
26608J. Porter and W. Sullivan, Nature Reviews Microbiology, 2023-07-10 13:14:07.
Wolbachia are successful Gram-negative bacterial endosymbionts, globally infecting a large fraction of arthropod species and filarial nematodes. Efficient vertical transmission, the capacity for horizontal transmission, manipulation of host reproduction and enhancement of host fitness can promote the spread both within and between species. Wolbachia are abundant and can occupy extraordinary diverse and evolutionary distant host species, suggesting that they have evolved to engage and manipulate highly conserved core cellular processes. Here, we review recent studies identifying Wolbachia–host interactions at the molecular and cellular levels. We explore how Wolbachia interact with a wide array of host cytoplasmic and nuclear components in order to thrive in a diversity of cell types and cellular environments. This endosymbiont has also evolved the ability to precisely target and manipulate specific phases of the host cell cycle. The remarkable diversity of cellular interactions distinguishes Wolbachia from other endosymbionts and is largely responsible for facilitating its global propagation through host populations. Finally, we describe how insights into Wolbachia–host cellular interactions have led to promising applications in controlling insect-borne and filarial nematode-based diseases.
Threshold dynamics of a stochastic mathematical model for Wolbachia infections
26546J. Yang, Z. Chen, Y. Tan, Z. Liu and R. A. Cheke, Journal of Biological Dynamics, 17:2231967. 2023-07-07 08:51:13.
A stochastic mathematical model is proposed to study how environmental heterogeneity and the augmentation of mosquitoes with Wolbachia bacteria affect the outcomes of dengue disease. The existence and uniqueness of the positive solutions of the system are studied. Then the V-geometrically ergodicity and stochastic ultimate boundedness are investigated. Further, threshold conditions for successful population replacement are derived and the existence of a unique ergodic steady-state distribution of the system is explored. The results show that the ratio of infected to uninfected mosquitoes has a great influence on population replacement. Moreover, environmental noise plays a significant role in control of dengue fever.
MGSurvE: A framework to optimize trap placement for genetic surveillance of mosquito population
26616C. H. Sánchez, D. L. Smith and J. M. Marshall, bioRxiv, 2023-06-23 13:35:51.
Genetic surveillance of mosquito populations is becoming increasingly relevant as genetics-based mosquito control strategies advance from laboratory to field testing. Especially applicable are mosquito gene drive projects, the potential scale of which leads monitoring to be a significant cost driver. For these projects, monitoring will be required to detect unintended spread of gene drive mosquitoes beyond field sites, and the emergence of alternative alleles, such as drive-resistant alleles or non-functional effector genes, within intervention sites. This entails the need to distribute mosquito traps efficiently such that an allele of interest is detected as quickly as possible - ideally when remediation is still viable. Additionally, insecticide-based tools such as bednets are compromised by insecticide-resistance alleles for which there is also a need to detect as quickly as possible. To this end, we present MGSurvE (Mosquito Gene SurveillancE): a computational framework that optimizes trap placement for genetic surveillance of mosquito populations such that the time to detection of an allele of interest is minimized. A key strength of MGSurvE is that it allows important biological features of mosquitoes and the landscapes they inhabit to be accounted for, namely: i) resources required by mosquitoes (e.g., food sources and aquatic breeding sites) can be explicitly distributed through a landscape, ii) movement of mosquitoes may depend on their sex, the current state of their gonotrophic cycle (if female) and resource attractiveness, and iii) traps may differ in their attractiveness profile. Example MGSurvE analyses are presented to demonstrate optimal trap placement for: i) an Aedes aegypti population in a suburban landscape in Queensland, Australia, and ii)an Anopheles gambiae population on the island of São Tomé, São Tomé and Príncipe. Further documentation and use examples are provided in project's documentation. MGSurvE is freely available as an open-source Python package on pypi ( https://pypi.org/project/MGSurvE/ ). It is intended as a resource for both field and computational researchers interested in mosquito gene surveillance. AUTHOR SUMMARY: Mosquito-borne diseases such as malaria and dengue fever continue to pose a major health burden throughout much of the world. The impact of currently-available tools, such as insecticides and antimalarial drugs, is stagnating, and gene drive-modified mosquitoes are considered a novel tool that could contribute to continuing reductions in disease transmission. Gene drive approaches are unique in the field of vector control in that they involve transgenes that could potentially spread on a wide scale, and consequently, surveillance is expected to be a major cost driver for the technology. This is needed to monitor for unintended spread of intact drive alleles, and the emergence of alternative alleles such as homing-resistance alleles and non-functional effector genes. Additionally, surveillance of insecticide-resistance alleles is of interest to support the impact of insecticide-based tools such as bednets. Here, we present MGSurvE, a computational framework that optimizes trap placement for genetic surveillance of mosquito populations in order to minimize the time to detection for an allele of interest. MGSurvE has been tailored to various features of mosquito ecology, and is intended as a resource for researchers to optimize the efficiency of limited surveillance resources.
CRISPR/Cas9-based gene drive could suppress agricultural pests
25706North Carolina State University, Phys Org, 2023-06-12 10:22:37.
Researchers have developed a "homing gene drive system" based on CRISPR/Cas9 that could be used to suppress populations of Drosophila suzukii vinegar flies—so-called "spotted-wing Drosophila" that devastate soft-skinned fruit in North America, Europe and parts of South America—according to new research from North Carolina State University. The NC State researchers developed dual CRISPR gene drive systems that targeted a specific D. suzukii gene called doublesex, which is important for sexual development in the flies. CRISPR stands for "clustered regularly interspaced short palindromic repeats" and Cas9 is an enzyme that performs like molecular scissors to cut DNA. CRISPR systems are derived from bacterial immune systems that recognize and destroy viruses and other invaders, and are being developed as solutions to problems in human, plant and animal health, among other uses. Targeting the doublesex gene resulted in female sterility in numerous experiments as females were unable to lay eggs, says Max Scott, an NC State entomologist who is the corresponding author of a paper in Proceedings of the National Academy of Sciences that describes the research. "This is the first so-called homing gene drive in an agricultural pest that potentially could be used for suppression," Scott said. Gene drives can preferentially select, change or delete particular traits or characteristics and "drive" those edits through future generations, resulting in a sometimes far greater than 50% chance of passing those changes to progeny.
Generation game: gene-edited mosquitos to fight malaria
25551J. Opara, Sci Dev Net, 2023-06-07 08:44:49.
Population-level changes in the genetic make-up of one of the world’s deadliest animals could provide a key in the fight against malaria, proponents of a radical new technology argue. So-called gene drive technology, where genetic changes are passed down through generations, could rein in mosquito populations, or prevent them from passing on malaria.“Through genetic engineering, researchers have modified mosquitoes to favour the inheritance of genes that either will reduce the size of the population of those mosquitoes or stop them from transmitting the malaria parasite,” Michael Santos, senior vice-president and chief population health sciences officer at the US-based charity the Foundation for the National Institutes of Health (FNIH), tells SciDev.Net. “In other words, [it is about] using mosquitoes to control mosquitoes.” Malaria is one of the world’s “big three” deadly diseases, killing over half a million people in 2021, the vast majority in Africa.
A framework for identifying fertility gene targets for mammalian pest control
25416C. C. Anna, A. Alana, E. Rey, E. Kevin, K. Sebastian, D. Ludovic, C. Jackson, E. C. Samuel, W. M. Philipp and J. G. Neil, bioRxiv, 2023.05.30.542751. 2023-06-01 07:38:46.
Fertility-targeted gene drives have been proposed as an ethical genetic approach for managing wild populations of vertebrate pests for public health and conservation benefit. This manuscript introduces a framework to identify and evaluate target gene suitability based on biological gene function, gene expression, and results from mouse knockout models. This framework identified 16 genes essential for male fertility and 12 genes important for female fertility that may be feasible targets for mammalian gene drives and other non-drive genetic pest control technology. Further, a comparative genomics analysis demonstrates the conservation of the identified genes across several globally significant invasive mammals. In addition to providing important considerations for identifying candidate genes, our framework and the genes identified in this study may have utility in developing additional pest control tools such as wildlife contraceptives.Competing Interest StatementThe authors have declared no competing interest.
The optimal strategy of incompatible insect technique (IIT) using Wolbachia and the application to malaria control
25203T. Matsufuji and S. Seirin-Lee, Journal of Theoretical Biology, 569:111519. 2023-05-29 09:18:33.
For decades, techniques to control vector population with low environmental impact have been widely explored in both field and theoretical studies. The incompatible insect technique (IIT) using Wolbachia, based on cytoplasmic incompatibility, is a technique that Wolbachia-infected male mosquitoes are incapable of producing viable offspring after mating with wild-type female mosquitoes. While the IIT method experimentally ensured its effectiveness in several field works, the failure of female mosquito population control by replacement owing to the accidental contamination of Wolbachia-infected female mosquitoes has been a concern and an obstacle in implementing the IIT method in nature. In this study, we develop a population-based IIT mathematical model using cytoplasmic incompatibility and evaluate the effectiveness of the IIT method in scenarios where contamination is present or absent. In addition, by extending the model to assess the disease infection status of the human population with malaria, we evaluate the optimal release strategy and cost for successful disease control. Our study proves that IIT could be a promising method to control mosquito-borne diseases without perfect suppression of vector mosquito population regardless of contamination.
Mosquito gene targeted RNAi studies for vector control
25650M. Yadav, N. Dahiya and N. Sehrawat, Functional and Integrative Genomics, 23:180. 2023-05-25 07:55:21.
Vector-borne diseases are serious public health concern. Mosquito is one of the major vectors responsible for the transmission of a number of diseases like malaria, Zika, chikungunya, dengue, West Nile fever, Japanese encephalitis, St. Louis encephalitis, and yellow fever. Various strategies have been used for mosquito control, but the breeding potential of mosquitoes is such tremendous that most of the strategies failed to control the mosquito population. In 2020, outbreaks of dengue, yellow fever, and Japanese encephalitis have occurred worldwide. Continuous insecticide use resulted in strong resistance and disturbed the ecosystem. RNA interference is one of the strategies opted for mosquito control. There are a number of mosquito genes whose inhibition affected mosquito survival and reproduction. Such kind of genes could be used as bioinsecticides for vector control without disturbing the natural ecosystem. Several studies have targeted mosquito genes at different developmental stages by the RNAi mechanism and result in vector control. In the present review, we included RNAi studies conducted for vector control by targeting mosquito genes at different developmental stages using different delivery methods. The review could help the researcher to find out novel genes of mosquitoes for vector control.
Targeting Sex Determination to Suppress Mosquito Populations
24988L. Ming, P. K. Nikolay, S. Ruichen, Y. Ting, D. B. Elena, J. B. Daniel, A. Igor, M. S. C. Hector, Z. Yinpeng, A. D. Nicolas, M. L. YuMin, P. S. Matthew, M. Craig, M. M. John and S. A. Omar, bioRxiv, 2023.04.18.537404. 2023-04-20 14:45:03.
Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Aedes aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to control wild populations, safely curtailing disease transmission.Competing Interest StatementO.S.A. is a founder of Agragene, Inc. with equity interest. O.S.A., M.L., and N.P.K are founders of Synvect with equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. All remaining authors declare no competing interests.
Modelling the effect of migration on the localisation and spread of a gene drive
24955C. Benjamin James and F.-L. Alexandre Jules Hen, bioRxiv, 2023.04.02.535303. 2023-04-04 14:22:19.
Gene drives have the potential to address pressing ecological issues. Through the super-Mendelian inheritance of a gene drive, a trait can be spread through a population even in spite of a fitness cost. This ability to spread is both its greatest quality and detractor. We may not want a gene drive to spread universally. If a gene drive were designed to cause the collapse of a pest population, it may inadvertently cause the collapse of the entire species. Migration is the mechanism through which a gene drive can spread to distant populations. Understanding its effect on the progression of a gene drive is crucial to our ability to control a gene drive. While migration can spread the gene drive to other populations, equally it can bring in other alleles to the population that may disrupt the progression of the gene drive. Through our deterministic migration gene drive model we can assess the conditions in which a gene drive is likely to spread to unintended populations, and if a gene drive is likely to be displaced by incoming alleles.Competing Interest StatementThe authors have declared no competing interest.
The Promise and Challenge of Genetic Biocontrol Approaches for Malaria Elimination
24901S. James and M. Santos, Tropical Medicine and Infectious Disease, 2023-03-29 07:50:09.
Malaria remains an ongoing public health challenge, with over 600,000 deaths in 2021, of which approximately 96% occurred in Africa. Despite concerted efforts, the goal of global malaria elimination has stalled in recent years. This has resulted in widespread calls for new control methods. Genetic biocontrol approaches, including those focused on gene-drive-modified mosquitoes (GDMMs), aim to prevent malaria transmission by either reducing the population size of malaria transmitting mosquitoes or making the mosquitoes less competent to transmit the malaria parasite. The development of both strategies has advanced considerably in recent years, with successful field trials of several biocontrol methods employing live mosquito products and demonstration of the efficacy of GDMMs in insectary-based studies. Live mosquito biocontrol products aim to achieve area-wide control with characteristics that differ substantially from current insecticide-based vector control methods, resulting in some different considerations for approval and implementation. The successful field application of current biocontrol technologies against other pests provides evidence for the promise of these approaches and insights into the development pathway for new malaria control agents. The status of technical development as well as current thinking on the implementation requirements for genetic biocontrol approaches are reviewed, and remaining challenges for public health application in malaria prevention are discussed.
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.
A mosquito population suppression model with a saturated Wolbachia release strategy in seasonal succession
24814Z. Zhang, L. Chang, Q. Huang, R. Yan and B. Zheng, J Math Biol, 86:51. 2023-03-06 08:55:06.
Releasing Wolbachia-infected male mosquitoes to suppress wild female mosquitoes through cytoplasmic incompatibility has shown great promise in controlling and preventing mosquito-borne diseases. To make the release logistically and economically feasible, we propose a saturated release strategy, which is only implemented during the epidemic season of mosquito-borne diseases. Under this assumption, the model becomes a seasonally switching ordinary differential equation model. The seasonal switch brings rich dynamics, including the existence of a unique periodic solution or exactly two periodic solutions, which are proved by using the qualitative property of the Poincaré map. Sufficient conditions are also obtained for determining the stability of the periodic solutions.
Wolbachia pipientis infections in populations of Aedes albopictus in the city of València (Spain): implications for mosquito control
24830R. Bueno-Marí, R. Domínguez-Santos, M. Trelis, E. Garrote-Sánchez, M. Cholvi, F. Quero de Lera, M. Khoubbane, A. Marcilla and R. Gi, Revista Española de Salud Pública, 97. 2023-03-02 16:20:52.
OBJECTIVE: The presence of Aedes albopictus, of high sanitary and social impact, was first reported in Valencia (Eastern Spain) in 2015. Innovative tools for its control include the use of the endosymbiotic bacterium Wolbachia pipientis. The release of mosquito males infected with the wPip strain, has proven very promising for large-scale Incompatible Insect Technique (IIT) applications. Before this strategy can be implemented in Valencia, it is important to know whether the natural local mosquito populations are Wolbachia-infected and, if so, identifying the infecting strains/supergroups, these being the objectives of the present work. METHODS: Eggs were collected from the 19 districts of the València city between May and October 2019. A total of 50 lab-reared adult Ae. albopictus individuals were processed and analyzed for Wolbachia detection and molecular characterization. These actions took place within the framework of a collaboration established with the Department of Health and Consumer Affairs of the city council of Valencia. Fisher's exact test was used to detect the statistical significance of the differences between groups. RESULTS: Our study revealed that 94% of the analyzed samples were naturally infected with Wolbachia. Both wAlbA and wAlbB supergroups were identified, with most samples (72% of the infected ones) carrying co-infections. CONCLUSIONS: These data provide the first characterization of the Wolbachia presence in natural populations of Ae. albopictus in the Mediterranean area of Spain. This information is relevant to evaluate the potential use of Wolbachia strains in order to achieve the suppression of the Asian tiger mosquito populations through massive release of artificially-infected males.
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.
Alleviating the burden of malaria with gene drive technologies? A biocentric analysis of the moral permissibility of modifying malaria mosquitoes
24800N. de Graeff, K. R. Jongsma and A. L. Bredenoord, Journal of Medical Ethics, 2023-02-28 08:33:28.
Gene drive technologies (GDTs) have been proposed as a potential new way to alleviate the burden of malaria, yet have also raised ethical questions. A central ethical question regarding GDTs relates to whether it is morally permissible to intentionally modify or eradicate mosquitoes in this way and how the inherent worth of humans and non-human organisms should be factored into determining this. Existing analyses of this matter have thus far generally relied on anthropocentric and zoocentric perspectives and rejected an individualist biocentric outlook in which all living organisms are taken to matter morally for their own sake. In this paper, we reconsider the implications of taking a biocentric approach and highlight nuances that may not be evident at first glance. First, we shortly discuss biocentric perspectives in general, and then outline Paul Taylor's biocentric theory of respect for nature. Second, we explore how conflicting claims towards different organisms should be prioritised from this perspective and subsequently apply this to the context of malaria control using GDTs. Our ethical analysis shows that this context invokes the principle of self-defence, which could override the pro tanto concerns that a biocentrist would have against modifying malaria mosquitoes in this way if certain conditions are met. At the same time, the case study of GDTs underlines the relevance of previously posed questions and criticism regarding the internal consistency of Taylor's egalitarian biocentrism.
Simulations Reveal High Efficiency and Confinement of a Population Suppression CRISPR Toxin-Antidote Gene Drive
24791Y. Zhu and J. Champer, ACS Synthetic Biolog, 2023-02-24 09:56:44.
Though engineered gene drives hold great promise for spreading through and suppressing populations of disease vectors or invasive species, complications such as resistance alleles and spatial population structure can prevent their success. Additionally, most forms of suppression drives, such as homing drives or driving Y chromosomes, will generally spread uncontrollably between populations with even small levels of migration. The previously proposed CRISPR-based toxin-antidote system called toxin-antidote dominant embryo (TADE) suppression drive could potentially address the issues of confinement and resistance. However, it is a relatively weak form of drive compared to homing drives, which might make it particularly vulnerable to spatial population structure. In this study, we investigate TADE suppression drive using individual-based simulations in a continuous spatial landscape. We find that the drive is actually more confined than in simple models without space, even in its most efficient form with low cleavage rate in embryos from maternally deposited Cas9. Furthermore, the drive performed well in continuous space scenarios if the initial release requirements were met, suppressing the population in a timely manner without being severely affected by chasing, a phenomenon in which wild-type individuals avoid the drive by recolonizing empty areas. At higher embryo cut rates, the drive loses its ability to spread, but a single, widespread release can often still induce rapid population collapse. Thus, if TADE suppression gene drives can be successfully constructed, they may play an important role in control of disease vectors and invasive species when stringent confinement to target populations is desired.
Gene Drive Technology With Agricultural Application Potential
24788R. Carmeli-Peslak, SeedWorld, 2023-02-22 09:51:36.
Gene drive technology, a genetic phenomenon that occurs in nature, causes a trait to spread in species through sexual reproduction over many generations. The inheritance rate is higher than the Mendelian rate which is 50%. Gene drives have been used for public health and conservation, but can potentially be used in multiple species, like agricultural pests according to a release. Weeds and pests have a negative impact on crops and their impact has caused interest in potentially using genetic techniques, like gene drive, to help control weeds and pests. Current insect pest control includes the use of pesticides which has helped to decrease food loss and waste. Research around new tools will help continue to protect crops and reduce food waste while also minimizing agriculture’s environmental footprint. These new tools and practices include gene editing techniques. Now in its early stages, gene-drive-based strategies are being research to help reduce agricultural pests. The gene-drive-based strategies will focus on both controlling pests that cause damage and spreading desired crop or livestock traits faster. A limitation with this strategy is that gene drives cannot work on asexually reproducing organisms. The strategy is also unsuitable for species that have longer generation times. While gene-drive-based strategies may not meet all the needs, but it is a helpful tool to continue to investigate.
Biopolitik: The Promise of Gene Drive
24708S. Todi, Technopolitik, 2023-02-07 09:57:49.
Gene drives are genetic elements of an organism that are transmitted to progeny at higher than mendelian frequencies (>50%). Gene editing techniques such as CRISPR–Cas9 have made gene drives extremely efficient in laboratory settings and have shown the potential to reduce the prevalence of vector-borne diseases, crop pests, and non-native invasive species. Research in gene drives, especially on mosquitoes, is being carried out by scientists at the University of California, San Diego, Texas A&M University, and Massachusetts Institute of Technology, among others. However, concerns have been raised regarding the potential unintended consequences, especially in terms of the ecological impact of gene-drive systems.
A Zika virus-responsive sensor-effector system in Aedes aegypti
24699S. Basu, C. M. Reitmayer, S. Lumley, B. Atkinson, M. L. Schade-Weskott, S. Rooney, W. Larner, E. E. Montiel, R. Gutierrez-Lopez, E. Levitt, H. M. Munyanduki, A. M. E. Elrefaey, A. T. Clarke, S. Koit, E. Zusinaite, R. Fragkoudis, A. Merits and L. Alphey, bioRxiv, 2023.02.06.527261. 2023-02-06 12:38:46.
Zika virus (ZIKV) is a recently re-emerged flavivirus transmitted primarily through the bite of an infected mosquito, Aedes aegypti being the main vector. ZIKV infection is associated with a range of adverse effects; infection during pregnancy can lead to foetal abnormalities, including microcephaly. Lacking a licensed vaccine, or specific therapeutics, control of ZIKV transmission focuses on vector control. However, in most transmission settings, current methods are insufficient to successfully control ZIKV, or other similarly-transmitted arboviruses such as dengue and chikungunya viruses. This has stimulated interest in genetics-based methods, either to reduce the number of mosquitoes (population suppression), or to make mosquitoes less able to transmit (population modification). Here, we describe a method to selectively eliminate infected mosquitoes, using a virus sensor inserted into the mosquito genome and coupled to a quorum-counting lethal effector. In mosquitoes, ZIKV normally establishes persistent, lifelong infection; survival of these infected mosquitoes is crucial to transmission potential. Correspondingly, removal of infected mosquitoes can reduce vectorial capacity of a mosquito population, i.e. ability to transmit. Since relatively few mosquitoes become infected, typically <2%, engineered hypersensitivity to ZIKV would have only a modest population-level fitness cost, and lower still if transmission were successfully reduced by such means.Competing Interest StatementThe authors have declared no competing interest.
Ethical dilemma: Should we get rid of mosquitoes?
24650Talya Hackett, TED-Ed, 2023-01-30 09:59:15.
Mosquitoes are responsible for more human deaths every year than any other animal, but very few of the 3,500 mosquito species actually transmit deadly diseases to humans. Scientists have been conducting experiments using engineered technologies called gene drives that could theoretically get rid of the most lethal mosquitoes. So, should we eradicate these pesky insects? Talya Hackett investigates.
Dynamics of an impulsive reaction-diffusion mosquitoes model with multiple control measures
24571Y. Li, H. Zhao and K. Wang, Mathematical Biosciences and Engineering, 20:775-806. 2023-01-14 08:34:08.
It is well-known that mosquito control is one of the effective methods to reduce and prevent the transmission of mosquito-borne diseases. In this paper, we formulate a reaction-diffusion impulsive hybrid model incorporating Wolbachia, impulsively spraying of insecticides, spatial heterogeneity, and seasonality to investigate the control of mosquito population. The sufficient conditions for mosquito extinction or successful Wolbachia persistence in a population of natural mosquitoes are derived. More importantly, we give the estimations of the spraying times of insecticides during a period for achieving the mosquito extinction and population replacement in a special case. A global attractivity of the positive periodic solution is analyzed under appropriate conditions. Numerical simulations disclose that spatial heterogeneity and seasonality have significant impacts on the design of mosquitoes control strategies. It is suggested to combine biological control and chemical pulse control under certain situations to reduce the natural mosquitoes. Further, our results reveal that the establishment of a higher level of population replacement depends on the strain type of the Wolbachia and the high initial occupancy of the Wolbachia-infected mosquitoes.
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.
CRISPR Gene Drives: A Weapon of Mass Destruction?
24336J. Ng, Medium, 2022-12-29 08:40:22.
Gene drives allow scientists to “drive” new genes — and their associated traits — into wildlife populations at unprecedented rates. Here’s a simplified explanation of how gene drives work. In normal sexual reproduction between species with two copies of chromosomes, each gene has a 50% chance of being inherited. However, there are particular DNA sequences called “selfish genes” whose frequency in the genome increases with each generation, even if this doesn’t result in an evolutionary advantage for the offspring. In 2003, biologist Austin Burt proposed a new way to use selfish genes to spread traits more efficiently through a population and ensure that offspring have a 100% probability of inheriting a particular DNA segment.
Gene drive designs for efficient and localisable population suppression using Y-linked editors
24339R. Geci, K. Willis and A. Burt, PLOS Genetics, 18:e1010550. 2022-12-27 08:45:03.
Author summary Some pest populations can be successfully controlled by the inundative release of sterile males, but this approach is not practicable when the target population is large or the species difficult to rear. Computer modelling has previously demonstrated that releasing males with a genomic editor on their Y chromosome that kills or sterilises female descendants could be much more efficient, particularly if combined with a sex ratio distorter. Here we extend this work to show that Y-linked editors can also be used in even more efficient gene drive designs that would spread over successive generations beyond the region of release. Such spread could nonetheless be controlled by exploiting relatively small pre-existing differences in gene frequency between populations to restrict the spread and impact of the constructs, if desired. The proposed design does not require high rates of recombinational repair of DNA breaks or expression off the Y chromosome during meiosis, potentially expanding the range of species in which such low release rate control is possible. Y-linked editors may therefore form the basis of a highly flexible set of genetic strategies for population control.
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.
Gene drive-mediated population elimination for biodiversity conservation. When you come to a fork in the road, take it
24281B. A. Hay and M. Guo, Proceedings of the National Academy of Sciences, 119:e2218020119. 2022-12-20 14:19:44.
How can the ability of t w2 to spread at super-Mendelian frequencies be utilized even if it is unable to directly drive the population to an unfit state? Gierus, Birand, and colleagues proposed placing Cas9 and a gRNA at a neutral position within the t haplotype. In this hybrid gene drive element, which they refer to as tCRISPR, Cas9 and the gRNA cleave and (hopefully) create loss-of-function (LOF) alleles in the male germ line of the prolactin (Prl) gene, which is required for female fertility. The goal with tCRISPR is for t-based segregation distortion in males to pump the Cas9/gRNAs cassette to high frequency within the population. The latter, through cleavage followed by inaccurate repair in males, will continuously produce LOF alleles at the independently segregating Prl locus. The hope is that the combination of t-based drive and accumulation of Prl LOF alleles will drive the population to an unfit state that contains a high frequency of infertile homozygous Prl mutant females along with some frequency of infertile homozygous t males. The combination of these two effects, they propose, could eliminate populations under a wider range of parameters than with t w2 alone
New CRISPR tech makes it possible to wipe out invasive mice
241812022-12-11 11:12:20.
Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control the human malaria mosquito vector Anopheles gambiae
24161A. Qureshi and J. B. Connolly, Malaria Journal, 2022-12-06 07:52:06.
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, (i) 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. Amino acid sequences of hCas9 and DsRed were interrogated against those of toxins or allergens from NCBI, UniProt, COMPARE and AllergenOnline bioinformatic databases and the gRNA was compared with microRNAs from the miRBase database for potential impacts on gene expression associated with toxicity or allergenicity. PubMed was also searched for any evidence of toxicity or allergenicity of Cas9 or DsRed, or of the donor organisms from which these products were originally derive While Cas9 nuclease activity can be toxic to some cell types in vitro and hCas9 was found to share homology with the prokaryotic toxin VapC, there was no evidence of a risk of toxicity to humans and other animals from hCas9. Although hCas9 did contain an 8-mer epitope found in the latex allergen Hev b 9, the full amino acid sequence of hCas9 was not homologous to any known allergens. Combined with a lack of evidence in the literature of Cas9 allergenicity, this indicated negligible risk to humans of allergenicity from hCas9. No matches were found between the gRNA and microRNAs from either Anopheles or humans. Moreover, potential exposure to dsxFCRISPRh transgenic proteins from environmental releases was assessed as negligible.Bioinformatic and literature assessments found no convincing evidence to suggest that transgenic products expressed from dsxFCRISPRh were allergens or toxins, indicating that environmental releases of this population suppression gene drive for malaria vector control should not result in any increased allergenicity or toxicity in humans or animals. These results should also inform evaluations of other GMMs being developed for vector control and in vivo clinical applications of CRISPR-Cas9.
A natural gene drive could steer invasive rodents on islands to extinction
24129B. Brookshire, ScienceNews, 2022-12-05 09:12:58.
In the battle against the invasive house mouse on islands, scientists are using the rodent’s own genes against it. With the right tweaks, introducing a few hundred genetically altered mice could drive an island’s invasive mouse population to extinction in about 25 years, researchers report in the Nov. 15 Proceedings of the National Academy of Sciences. The trick is adding the changes to a section of mouse DNA that gets inherited far more often than it should. Scientists have been creating similar extra-inheritable genes — called gene drives — in the lab. The chunks are designed to get passed on to most or all of an animal’s offspring instead of the usual half, and make those offspring infertile in the bargain. Scientists have used gene drives to reduce populations of mosquitoes and fruit flies (SN: 12/17/18). But mammals are a different story. Scientists have previously synthesized a gene drive that gets passed on in mice about 80 percent of the time (SN: 1/23/19). But the drive isn’t strong enough to stop a population quickly. Luckily, nature has it handled. A haplotype is a naturally occurring group of genes that gets passed on as a unit during replication. The genome of the house mouse (Mus musculus) has a particular haplotype, called the t haplotype, that gets passed on to offspring more than 95 percent of the time, instead of the typical 50 percent.
Should NZ use contentious gene tech in our war on pests?
24032J. Morton, NZ Herald, 2022-11-27 09:45:02.
Gene-altering technology could offer “breakthrough opportunities” for saving our pest-threatened species, a new future-scoping report says, but there’d be some tricky issues to address before it’d be a realistic option. Scientists have already been exploring how these contentious tools - among several areas canvassed in a new future-focused briefing by the Department of Conservation and Land Information New Zealand - might aid our ongoing war on pest predators. But it’s doubtful that would happen anytime soon, given the tech isn’t yet ready, and the Government has little appetite toward making law changes that’d likely be needed to unleash it in our environment. The briefing, just put out for public feedback, explained how gene-editing tools like Crispr-Cas9 could be used to change particular genes or introduce new traits.
The effect of mating complexity on gene drive dynamics
23967P. Verma, R. G. Reeves, S. Simon, M. Otto and C. S. Gokhale, The American Naturalist, 2022-11-15 12:33:47.
Gene drive technology promises to deliver on some of the global challenges humanity faces today in health care, agriculture, and conservation. However, there is a limited understanding of the consequences of releasing self-perpetuating transgenic organisms into wild populations under complex ecological conditions. In this study, we analyze the impact of three such complexities—mate choice, mating systems, and spatial mating network—on the population dynamics for two distinct classes of modification gene drive systems. All three factors had a high impact on the modeling outcome. First, we demonstrate that distortion-based gene drives appear to be more robust against mate choice than viability-based gene drives. Second, we find that gene drive spread is much faster for higher degrees of polygamy. Including a fitness cost, the drive is fastest for intermediate levels of polygamy. Finally, the spread of a gene drive is faster and more effective when the individuals have fewer connections in a spatial mating network. Our results highlight the need to include mating complexities when modeling the properties of gene drives, such as release thresholds, timescales, and population-level consequences. This inclusion will enable a more confident prediction of the dynamics of engineered gene drives and possibly even inform about the origin and evolution of natural gene drives.
Independent evaluation of Wolbachia infected male mosquito releases for control of Aedes aegypti in Harris County, Texas, using a Bayesian abundance estimator
23969S. Lozano, K. Pritts, D. Duguma, C. Fredregill and R. Connelly, PLOS Neglected Tropical Diseases, 16:e0010907. 2022-11-14 12:37:36.
Among disease vectors, Aedes aegypti (L.) (Diptera: Culicidae) is one of the most insidious species in the world. The disease burden created by this species has dramatically increased in the past 50 years, and during this time countries have relied on pesticides for control and prevention of viruses borne by Ae. aegypti. The small number of available insecticides with different modes of action had led to increases in insecticide resistance, thus, strategies, like the “Incompatible Insect Technique” using Wolbachia’s cytoplasmic incompatibility are desirable. We evaluated the effect of releases of Wolbachia infected Ae. aegypti males on populations of wild Ae. aegypti in the metropolitan area of Houston, TX. Releases were conducted by the company MosquitoMate, Inc. To estimate mosquito population reduction, we used a mosquito abundance Bayesian hierarchical estimator that accounted for inefficient trapping. MosquitoMate previously reported a reduction of 78% for an intervention conducted in Miami, FL. In this experiment we found a reduction of 93% with 95% credibility intervals of 86% and 96% after six weeks of continual releases. A similar result was reported by Verily Life Sciences, 96% [94%, 97%], in releases made in Fresno, CA.
Gene drive could be used to wipe out invasive mice on islands
23862M. Le Page, NewScientist, 2022-11-11 10:11:35.
For the first time, researchers have created a gene drive – a kind of genetic parasite – that could be used to eradicate mammalian pests such as mice by making them infertile. The technology could provide a humane alternative to the poison baits currently used to tackle invasive mice on islands, which have severe impacts on native birds, reptiles and plants. “It’s the first example of a mammalian gene drive technology that has had proof of concept in a laboratory setting,” says Paul Thomas at the University of Adelaide in Australia. Most animals have two copies of each chromosome, but their offspring gets only one copy from each parent. This means that if a piece of DNA is added to one chromosome of an individual, only half its offspring will inherit it. Gene drives are bits of DNA that encode various mechanisms for cheating the system and ensuring they get inherited by more than half of offspring. This means they can spread in a population even if they are harmful. Various kinds of natural gene drives have been discovered. In 2013, Kevin Esvelt at Massachusetts Institute of Technology created the first synthetic gene drive using the gene-editing technology CRISPR. Such CRISPR-based gene drives work extremely well in insects and several teams hope to use them to prevent the spread of malaria, either by wiping out mosquitoes or by making them less likely to infect people.
World first trial to eradicate mice through gene modification
23838I. Mannix, COSMOS, 2022-11-10 09:51:29.
Mouse populations could be eradicated in some areas through new gene modification technology to render female mice infertile. The technology – called t-CRISPR – was previously developed to target malaria-transmitting mosquitoes. This is the first proof of concept for its use as a mammalian genetic biocontrol tool targeting house mice, which is an invasive pest in Australia. In time, it could be used to control rodents on islands and landmasses where they cause widespread destruction. The research, published in Proceedings of the National Academy of Sciences, is the first time t-CRISPR has been successfully tested on mammals in a laboratory setting, according to senior author Professor Paul Thomas. Computer modelling conducted by the team suggests about 250 gene-modified mice could eradicate an island population of 200,000 mice in around 20 years. “We have had mouse plagues in Australia for 150 years and existing controls, like baits, cause inhumane death and are expensive and labour intensive to deploy,” says Thomas, who works across the University of Adelaide and the South Australian Health and Medical Research Institute.
Gene drive technology to suppress invasive mice
23843University of Adelaide, Phys Org, 2022-11-09 09:55:57.
Researchers at the University of Adelaide have released their first findings on the potential effectiveness of revolutionary gene drive technology to control invasive mice. The team has developed a world-first proof of concept for the technology—called t-CRISPR—using laboratory mice. Using sophisticated computer modeling performed by co-first author Dr. Aysegul Birand, the researchers also found about 250 gene-modified mice could eradicate an island population of 200,000 mice in around 20 years. The results of the study have been published today in Proceedings of the National Academy of Sciences.
Leveraging a natural murine meiotic drive to suppress invasive populations
23835L. Gierus, A. Birand, M. D. Bunting, G. I. Godahewa, S. G. Piltz, K. P. Oh, A. J. Piaggio, D. W. Threadgill, J. Godwin, O. Edwards, P. Cassey, J. V. Ross, T. A. A. Prowse and P. Q. Thomas, Proceedings of the National Academy of Sciences, 119:e2213308119. 2022-11-08 09:36:13.
Invasive rodents are a major cause of environmental damage and biodiversity loss, particularly on islands. Unlike insects, genetic biocontrol strategies including population-suppressing gene drives with biased inheritance have not been developed in mice. Here, we demonstrate a gene drive strategy (t(CRISPR)) that leverages super-Mendelian transmission of the t haplotype to spread inactivating mutations in a haplosufficient female fertility gene (Prl). Using spatially explicit individual-based in silico modeling, we show that t(CRISPR) can eradicate island populations under a range of realistic field-based parameter values. We also engineer transgenic t(CRISPR) mice that, crucially, exhibit biased transmission of the modified t haplotype and Prl mutations at levels our modeling predicts would be sufficient for eradication. This is an example of a feasible gene drive system for invasive alien rodent population control.
Monotonicity properties arising in a simple model of Wolbachia invasion for wild mosquito populations
24568D. Vicencio, O. Vasilieva and P. Gajardo, Mathematical Biosciences and Engineering, 20:1148-1175. 2022-10-25 08:23:57.
Using tools borrowed from monotone dynamical system theory, in the proposed model, we prove the existence of an invariant threshold manifold that allows us to provide practical recommendations for performing single and periodic releases of Wolbachia-carrying mosquitoes, seeking the eventual elimination of wild insects that are capable of transmitting infections to humans. We illustrate these findings with numerical simulations using parameter values corresponding to the wMelPop strain of Wolbachia that is considered the best virus blocker but induces fitness loss in its carriers. In these tests, we considered multiple scenarios contrasting a periodic release strategy against a strategy with a single inundative release, comparing their effectiveness. Our study is presented as an expository and mathematically accessible tool to study the use of Wolbachia-based biocontrol versus more complex models.
Why we need to talk about ‘gene-drive’ grey squirrels
23778Anonymous, University of Exeter, 2022-10-17 07:04:37.
Would the best way of controlling the UK’s rampant grey squirrel population be to spread genetic changes throughout the species? A new research film, to be shown next month at Exeter Phoenix, sees scientists, conservation and wildlife experts debate the use of emergent ‘gene-drive’ technology in grey squirrels. The film Should we create gene drive grey squirrels?, written and produced by Sarah Hartley, a Professor in Technology Governance at the University of Exeter Business School, and independent film-maker Tom Law, documents the introduction into the UK of grey squirrels at the turn of the 20th Century and how their burgeoning population has contributed to the demise of the UK’s native red squirrel, which is now mainly found in Scotland. It presents the reasons why some people argue it would be better to limit the grey squirrel population, including the fact that they carry and spread squirrel pox, a virus fatal to red squirrels which can devastate entire populations.
GeneConvene Global Collaborative Webinar Series | Wolbachia Biology, Mechanisms and Applications 2022
23723David O'Brochta, GeneConvene Global Collaborative, 2022-10-15 06:57:26.
Intracellular and extracellular symbiotic/commensal bacteria have enormous potential when manipulated and deployed appropriately to serve as agents of control of insects and the pathogens they transmit. Wolbachia, an intracellular bacteria, is a well studied system and one that is used increasingly to control insect populations via cytoplasmic incompatibility and to alter the vectoral capacity of insect via pathogen inhibition. This webinar series will survey the applications of Wolbachia as a mosquito/dengue control intervention and the underlying biology that conditions its effectiveness.
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.
Wolbachia strain wAlbB remains stable in Aedes aegypti over 15 years but exhibits genetic background-dependent variation in virus blocking
23646X. Liang, C. H. Tan, Q. Sun, M. Zhang, P. J. Wong, M. I. Li, et al., PNAS Nexus, 2022-09-22 08:20:54.
The ability of the maternally transmitted endosymbiotic bacterium Wolbachia to induce cytoplasmic incompatibility (CI) and virus blocking makes it a promising weapon for combatting mosquito-borne diseases through either suppression or replacement of wild-type populations. Recent field trials show that both approaches significantly reduce the incidence of dengue fever in humans. However, new questions emerge about how Wolbachia-mosquito associations will co-evolve over time and whether Wolbachia-mediated virus blocking will be affected by the genetic diversity of mosquitoes and arboviruses in the real world. Here, we have compared the Wolbachia density and CI expression of two wAlbB-infected Aedes aegypti lines transinfected 15 years apart. We have also assessed wAlbB-mediated virus blocking against dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) viruses and examined whether host genetic backgrounds modulate viral blocking effects by comparing ZIKV infection in mosquitoes with a Mexican genetic background to those with a Singaporean background. Our results show that over 15 years, wAlbB maintained the capacity to form a stable association with Ae. aegypti in terms of both density and CI expression. There were variations in wAlbB-induced virus blocking against CHIKV, DENV, and ZIKV, and higher inhibitory effects on ZIKV in mosquitoes on the Singaporean genetic background than on the Mexican background. These results provide important information concerning the robustness and long-term stability of Wolbachia as a biocontrol agent for arbovirus disease control.
Applications of gene drive systems for population suppression of insect pests
23503M. Asad, D. Liu, J. Chen and G. Yang, Bulletin of Entomological Research, 2022-08-31 19:19:28.
Population suppression is an effective way for controlling insect pests and disease vectors, which cause significant damage to crop and spread contagious diseases to plants, animals and humans. Gene drive systems provide innovative opportunities for the insect pests population suppression by driving genes that impart fitness costs on populations of pests or disease vectors. Different gene-drive systems have been developed in insects and applied for their population suppression. Here, different categories of gene drives such as meiotic drive (MD), under-dominance (UD), homing endonuclease-based gene drive (HEGD) and especially the CRISPR/Cas9-based gene drive (CCGD) were reviewed, including the history, types, process and mechanisms. Furthermore, the advantages and limitations of applying different gene-drive systems to suppress the insect population were also summarized. This review provides a foundation for developing a specific gene-drive system for insect population suppression.
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.
World Mosquito Day: Can genetic modification techniques quash the menace?
23446CNBCTV18, CNBC TV18, 2022-08-20 09:54:03.
Genetically modified (GM) mosquitoes are prepared in labs and are supposed to fight the Aedes aegypti mosquitoes which spread viruses including dengue, Zika, and chikungunya. Billions have apparently been successfully released in the US, Brazil, the Cayman Islands, Panama, and India.
Precision Guided Sterile Males Suppress Populations of an Invasive Crop Pest
23453N. P. Kandul, J. Liu, A. Buchman, I. C. Shriner, R. M. Corder, N. Warsinger-Pepe, T. Yang, A. K. Yadav, M. J. Scott, J. M. Marshall and O. S. Akbari, GEN Biotechnology, 1:372-385. 2022-08-18 10:24:32.
The Drosophila suzukii invasion of western countries has created an immense agricultural and economic threat to crop production. Despite many attempts to suppress its population, D. suzukii continues to destroy soft-flesh fruits. Precision guided sterile insect technique (pgSIT) utilizes the accuracy of programmable CRISPR gene targeting to generate sterilized males that can be deployed to suppress populations. Here, we generate pgSIT in D. suzukii and empirically and mathematically demonstrate that sterilized males are fit, competitive, and can eliminate populations of D. suzukii. Altogether, we describe an efficient way to generate sterile D. suzukii for release and safe effective population suppression.
A theory of resistance to multiplexed gene drive demonstrates the significant role of weakly deleterious natural genetic variation
23362B. S. Khatri and A. Burt, Proceedings of the National Academy of Sciences, 119:e2200567119. 2022-08-01 07:26:58.
CRISPR-based gene drives have the potential for controlling natural populations of disease vectors, such as malaria-carrying mosquitoes in sub-Saharan Africa. If successful, they hold promise of significantly reducing the burden of disease and death from malaria and many other vector-borne diseases. A significant challenge to success is the evolution of resistance. Here, we develop a theory of resistance for multiplexed drive, which shows the importance of weakly deleterious naturally occurring genetic variation, whose effect is significantly amplified compared to de novo mutation. These results provide a fundamental basis to estimate how many guide RNAs are required to prevent resistance in the face of natural genetic variation. Evolution of resistance is a major barrier to successful deployment of gene-drive systems to suppress natural populations, which could greatly reduce the burden of many vector-borne diseases. Multiplexed guide RNAs (gRNAs) that require resistance mutations in all target cut sites are a promising antiresistance strategy since, in principle, resistance would only arise in unrealistically large populations. Using stochastic simulations that accurately model evolution at very large population sizes, we explore the probability of resistance due to three important mechanisms: 1) nonhomologous end-joining mutations, 2) single-nucleotide mutants arising de novo, or 3) single-nucleotide polymorphisms preexisting as standing variation. Our results explore the relative importance of these mechanisms and highlight a complexity of the mutation?selection?drift balance between haplotypes with complete resistance and those with an incomplete number of resistant alleles. We find that this leads to a phenomenon where weakly deleterious naturally occurring variants greatly amplify the probability of multisite resistance compared to de novo mutation. This key result provides design criterion for antiresistance multiplexed systems, which, in general, will need a larger number of gRNAs compared to de novo expectations. This theory may have wider application to the evolution of resistance or evolutionary rescue when multiple changes are required before selection can act.
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
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.
Gene drives and Africa’s battle against malaria
23154Annonymous, Africa Verified, 2022-07-08 09:43:10.
As malaria cases rise, and the effectiveness of current methods begins to fall, the WHO’s target of reducing the global malaria burden by 90% by 2030 will not be met. It is critical for new and resilient treatment, prevention, and control methods to be developed and integrated into current strategies. Target Malaria is a not-for-profit research consortium aiming to develop ‘cost-effective and sustainable genetic technologies to modify mosquitoes and reduce malaria transmission’ that would work alongside current anti-malaria efforts. They are pioneering research into genetically programmed mosquitoes, which when released into the wild to mate, reproduce offspring that either produce fewer female mosquitoes or are unable to transmit malaria parasites.
Slow and steady wins the race: spatial and stochastic processes and the failure of suppression gene drives
23117J. F. Paril and B. L. Phillips, Molecular Ecology, 2022-07-05 08:47:10.
Gene drives that skew sex ratios offer a new management tool to suppress or eradicate pest populations. Early models and empirical work suggest that these suppression drives can completely eradicate well-mixed populations, but models that incorporate stochasticity and space (i.e., drift, and recolonization events) often result in loss or failure of the drive. We developed a stochastic model to examine these processes in a simple 1-dimensional space. This simple space allows us to map the events and outcomes that emerged and examine how properties of the drive's wave of invasion affect outcomes. Our simulations, across a biologically-realistic section of parameter space, suggest that drive failure might be a common outcome in spatially explicit, stochastic systems, and that properties of the drive wave appear to mediate outcomes. Surprisingly, the drives that would be considered fittest in an aspatial model were strongly associated with failure in the spatial setting. The fittest drives cause relatively fast moving, and narrow waves that have a high chance of being penetrated by wild-types leading to wild-type recolonization, leading to failure. Our results also show that high rates of dispersal reduce the chance of failure because drive waves get disproportionately wider than wild-type waves as dispersal rates increase. Overall, wide, slow-moving drive waves were much less prone to failure. Our results point to the complexity inherent in using a genetic system to effect demographic outcomes and speak to a clear need for ecological and evolutionary modelling to inform the drive design process.
Partial masculinization of Aedes aegypti females by conditional expression of Nix
23113B. B. Kojin, E. Jakes, J. K. Biedler, Z. Tu and Z. N. Adelman, PLOS Neglected Tropical Diseases, 16:e0010598. 2022-07-01 08:17:41.
Here, we report on the conditional expression of Nixin transgenic A. aegypti under the control of the tetracycline-dependent (Tet-off) system, with the goal of establishing repressible sex distortion. A masculinization phenotype was observed in three of the seven transgenic lines with females exhibiting male-like long maxillary palps and most importantly, the masculinized females were unable to blood feed. Doxycycline treatment of the transgenic lines only partially restored the normal phenotype from the masculinized transgenic lines, while RT-qPCR analysis of early embryos or adults showed no correlation between the level of masculinization and ectopic Nix expression. While the conditional expression of Nix produced intersex phenotypes, the level of expression was insufficient to program full conversion. Modifications that increase both the level of activation (no tet) and the level of repression (with tet) will be necessary, as such this study represents one step forward in the development of genetic strategies to control vector-borne diseases via sex ratio distortion.
Public perspectives towards using gene drive for invasive species management in Australia
23100A. Mankad, E. V. Hobman and L. Carter, CSIRO, 2022-06-30 07:55:31.
Many pest animal species live and reproduce in high numbers across Australia. This includes animal species, such as cane toads, feral cats, foxes, rodents, wild pigs, wild rabbits. These species significantly damage Australia’s agricultural industries, natural landscapes, and biodiversity. For example, feral cats kill an estimated 1.8 billion Australian animals every year. Feral animals can also carry livestock diseases and cause significant damage to land and native vegetation. This results in agricultural production losses of more than $800 million per year. Sites of cultural significance to Indigenous peoples are also at risk to pest incursions. Adding further complexity, current methods of pest control being used to manage local landscape, such as baiting, trapping and shooting, are labour-intensive and expensive. They also have animal welfare implications and are considered ineffective at scale. Genetic technologies that are developed using synthetic biology have the potential to reduce or in some cases eliminate populations of invasive pests in parts of Australia. But there are multiple social, cultural and institutional considerations to understand before genetic technologies could feasibly be integrated with current pest management practices.
Manipulating Insect Sex Determination Pathways for Genetic Pest Management: Opportunities and Challenges
23084A. Siddall, T. Harvey-Samuel, T. Chapman and P. T. Leftwich, Frontiers in Bioengineering and Biotechnology, 10. 2022-06-28 07:14:08.
Sex determination pathways in insects are generally characterised by an upstream primary signal, which is highly variable across species, and that regulates the splicing of a suite of downstream but highly-conserved genes (transformer, doublesex and fruitless). In turn, these downstream genes then regulate the expression of sex-specific characteristics in males and females. Identification of sex determination pathways has and continues to be, a critical component of insect population suppression technologies. For example, “first-generation” transgenic technologies such as fsRIDL (Female-Specific Release of Insects carrying Dominant Lethals) enabled efficient selective removal of females from a target population as a significant improvement on the sterile insect technique (SIT). Second-generation technologies such as CRISPR/Cas9 homing gene drives and precision-guided SIT (pgSIT) have used gene editing technologies to manipulate sex determination genes in vivo. The development of future, third-generation control technologies, such as Y-linked drives, (female to male) sex-reversal, or X-shredding, will require additional knowledge of aspects of sexual development, including a deeper understanding of the nature of primary signals and dosage compensation. This review shows how knowledge of sex determination in target pest species is fundamental to all phases of the development of control technologies.
The AalNix3&4 isoform is required and sufficient to convert Aedes albopictus females into males
23070Y. Zhao, B. Jin, P. Liu, X. Xiao, L. Cai, Z. Xie, L. Kong, T. Liu, W. Yang, Y. Wu, J. Gu, Z. Tu, A. A. James and X.-G. Chen, PLOS Genetics, 18:e1010280. 2022-06-23 08:45:44.
Author summary Nix serves as a conserved male-determining factor in the two most important mosquito arboviral vectors, Ae. aegypti and Ae. albopictus. AaeNix alone can convert Ae. aegypti females into fertile but flightless males. AalNix has four alternative splice isoforms whereas AaeNix has one. Little was known previously about which AalNix isoform(s) serve as the primary signal for sex determination. We cloned the promoter region of AalNix gene and constructed piggybac-based AalNix overexpression constructs with different isoform variants. Following transformation and recovery of transgenic lines, we observed that expression of the AalNix3&4 isoform could shift the alternative splicing of the sex determination genes, doublesex and fruitless, from female to male isoforms, and phenotypically masculinize females or completely convert females into males. Importantly, the sex-converted pseudo-males are fertile and capable of flight. Thus, AalNix is the primary signal for male sex determination in Aedes albopictus and provides a basis for sex segregation and further Cas9-mediated gene-drive population suppression.
Natural and Engineered Sex Ratio Distortion in Insects
23010A. Compton and Z. Tu, Frontiers in Ecology and Evolution, 10. 2022-06-15 08:25:52.
Insects have evolved highly diverse genetic sex-determination mechanisms and a relatively balanced male to female sex ratio is generally expected. However, selection may shift the optimal sex ratio while meiotic drive and endosymbiont manipulation can result in sex ratio distortion (SRD). Recent advances in sex chromosome genomics and CRISPR/Cas9-mediated genome editing brought significant insights into the molecular regulators of sex determination in an increasing number of insects and provided new ways to engineer SRD. We review these advances and discuss both naturally occurring and engineered SRD in the context of the Anthropocene. We emphasize SRD-mediated biological control of insects to help improve One Health, sustain agriculture, and conserve endangered species.
Selective targeting of biting females to control mosquito-borne infectious diseases
22953B. B. Kojin, A. Compton, Z. N. Adelman and Z. Tu, Trends in Parasitology, 2022-06-13 06:48:00.
Mosquitoes are vectors for a number of infectious diseases. Only females feed on blood to provision for their embryos and, in doing so, transmit pathogens to the associated vertebrate hosts. Therefore, sex is an important phenotype in the context of genetic control programs, both for sex separation in the rearing facilities to avoid releasing biting females and for ways to distort the sex ratio towards nonbiting males. We review recent progress in the fundamental knowledge of sex determination and sex chromosomes in mosquitoes and discuss new methods to achieve sex separation and sex ratio distortion to help control mosquito-borne infectious diseases. We conclude by suggesting a few critical areas for future research.
Mendel’s First Law: partisan interests and the parliament of genes
23006C. Veller, Heredity, 2022-06-11 07:51:41.
Mendel’s First Law requires explanation because of the possibility of ‘meiotic drivers’, genes that distort fair segregation for selfish gain. The suppression of drive, and the restoration of fair segregation, is often attributed to genes at loci unlinked to the drive locus—such genes cannot benefit from drive but do suffer its associated fitness costs. However, selection can also favour suppressors at loci linked to the drive locus, raising the question of whether suppression of drive usually comes from linked or unlinked loci. Here, I study linked and unlinked suppression in a two-locus model with initial stable polymorphism at the drive locus. I find that the invasion rate of suppressors is a decreasing function of the recombination fraction between the drive and suppressor loci. Surprisingly, the relative likelihood of unlinked vs. linked suppression increases with the strength of drive and is insensitive to the fitness costs of the driver allele. I find that the chromosomal position of the driver influences how rapidly it is suppressed, with a driver in the middle of a chromosome suppressed more rapidly than a driver near the tip. When drive is strong, only a small number of chromosomes are required for suppression usually to derive from unlinked loci. In contrast, when drive is weak, and especially when suppressor alleles are associated with fitness costs, suppression will usually come from linked loci unless the genome comprises many chromosomes.
Wolbachia interacts with the microbiome to shape fitness-associated traits during seasonal adaptation in Drosophila melanogaster
22693L. P. Henry, M. Fernandez, S. Wolf and J. Ayroles, bioRxiv, 2022.05.31.494239. 2022-06-01 14:39:02.
The microbiome contributes to many different host traits, but its role in host adaptation remains enigmatic. The fitness benefits of the microbiome often depend on ecological conditions, but fluctuations in both the microbiome and environment modulate these fitness benefits. Moreover, vertically transmitted bacteria might constrain the ability of both the microbiome and host to respond to changing environments. Drosophila melanogaster provides an excellent system to investigate the evolutionary effects of interactions between the microbiome and the environment. To address this question, we created field mesocosms of D. melanogaster undergoing seasonal adaptation with and without the vertically transmitted bacteria, Wolbachia pipientis. Sampling temporal patterns in the microbiome revealed that Wolbachia constrained microbial diversity. Furthermore, interactions between Wolbachia and the microbiome contributed to fitness-associated traits. Wolbachia often exerted negative fitness effects on hosts, and the microbiome modulated these effects. Our work supports recent theoretical advances suggesting that hosts in temporally fluctuating environments benefit from flexible microbial associations with low transmission fidelity--specifically when changes in the microbiome can better enable host phenotypes to match environment change. We conclude by exploring the consequences of complex interactions between Wolbachia and the microbiome for our understanding of eco-evolutionary processes and the utility of Wolbachia in combating vector-borne disease.Competing Interest StatementThe authors have declared no competing interest.
Recommendations for environmental risk assessment of gene drive applications for malaria vector control
22586J. B. Connolly, J. D. Mumford, D. C. M. Glandorf, S. Hartley, O. T. Lewis, S. W. Evans, G. Turner, C. Beech, N. Sykes, M. B. Coulibaly, J. Romeis, J. L. Teem, W. Tonui, B. Lovett, A. Mankad, A. Mnzava, S. Fuchs, T. D. Hackett, W. G. Landis, J. M. Marshall, Malar J, 21:152. 2022-05-25 09:36:02.
Building on an exercise that identified potential harms from simulated investigational releases of a population suppression gene drive for malaria vector control, a series of online workshops identified nine recommendations to advance future environmental risk assessment of gene drive applications.
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.
Strategies to Mitigate Establishment under the Wolbachia Incompatible Insect Technique
23104S. Soh, S. H. Ho, J. Ong, A. Seah, B. S. Dickens, K. W. Tan, J. R. Koo, A. R. Cook, S. Sim, C. H. Tan, L. C. Ng and J. T. Lim, Viruses, 14. 2022-05-24 08:10:53.
The Incompatible Insect Technique (IIT) strategy involves the release of male mosquitoes infected with the bacterium Wolbachia. Regular releases of male Wolbachia-infected mosquitoes can lead to the suppression of mosquito populations, thereby reducing the risk of transmission of vector-borne diseases such as dengue. However, due to imperfect sex-sorting under IIT, fertile Wolbachia-infected female mosquitoes may potentially be unintentionally released into the environment, which may result in replacement and failure to suppress the mosquito populations. As such, mitigating Wolbachia establishment requires a combination of IIT with other strategies. We introduced a simple compartmental model to simulate ex-ante mosquito population dynamics subjected to a Wolbachia-IIT programme. In silico, we explored the risk of replacement, and strategies that could mitigate the establishment of the released Wolbachia strain in the mosquito population. Our results suggest that mitigation may be achieved through the application of a sterile insect technique. Our simulations indicate that these interventions do not override the intended wild type suppression of the IIT approach. These findings will inform policy makers of possible ways to mitigate the potential establishment of Wolbachia using the IIT population control strategy.
Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models
22288Y. Liu, W. Teo, H. Yang and J. Champer, bioRxiv, 2022.05.08.491087. 2022-05-08 08:15:29.
Suppression gene drives are designed to bias their inheritance and increase in frequency in a population, disrupting an essential gene in the process. When the frequency is high enough, the population will be unable to reproduce above the replacement level and could be eliminated. CRISPR suppression drives based on the homing mechanism have already seen success in the laboratory, particularly in malaria mosquitoes. However, several models predict that the use of these drives in realistic populations with spatial structure may not achieve complete success. This is due to the ability of wild-type individuals to escape the drive and reach empty areas with reduced competition, allowing them to achieve high reproductive success and leading to extinction-recolonization cycles across the landscape. Here, we extend our continuous space gene drive framework to include two competing species or predator-prey species pairs. We find in both discrete-generation and mosquito-specific models that the presence of a competing species or predator can greatly facilitate drive-based suppression, even for drives with modest efficiency. However, the presence of a competing species also substantially increases the frequency of outcomes in which the drive is lost before suppression is achieved. These results are robust in models with seasonal population fluctuations. We also found that suppression can be somewhat more difficult if targeting a predator with strong predator-prey interactions. Our results illustrate the difficulty of predicting outcomes of interventions that could substantially affect the populations of interacting species in complex ecosystems. However, our results are also potentially promising for the prospects of less powerful gene drives in achieving successful elimination of target pest populations.Competing Interest StatementThe authors have declared no competing interest.
The fate of a suppressed X-linked meiotic driver: experimental evolution in Drosophila simulans
22676H. Bastide, D. Ogereau, C. Montchamp-Moreau and P. R. Gérard, Chromosome Research, 2022-04-30 07:53:46.
Sex-ratio (SR) meiotic drivers are X-linked selfish genetic elements that promote their own transmission by preventing the production of Y-bearing sperm, which usually lowers male fertility. The spread of SR drivers in populations is expected to trigger the evolution of unlinked drive suppressors, a theoretically predicted co-evolution that has been observed in nature. Once completely suppressed, the drivers are expected either to decline if they still affect the fitness of their carriers, or to evolve randomly and possibly get fixed if the suppressors eliminate their deleterious effects. To explore this issue, we used the Paris sex-ratio system of Drosophila simulans in which drive results from the joint effect of two elements on the X chromosome: a segmental duplication and a deficient allele of the HP1D2 gene. We set up six experimental populations starting with 2/3 of X chromosomes carrying both elements (X(SR)) in a fully suppressing background. We let them evolve independently during almost a hundred generations under strong sexual competition, a condition known to cause the rapid disappearance of unsuppressed Paris X(SR) in previous experimental populations. In our study, the fate of X(SR) chromosomes varied among populations, from extinction to their maintenance at a frequency close to the starting one. While the reasons for these variable outcomes are still to be explored, our results show that complete suppression can prevent the demise of an otherwise deleterious X(SR) chromosome, turning a genetic conflict into cooperation between unlinked loci. Observations in natural populations suggest a contrasting fate of the two elements: disappearance of the duplication and maintenance of deficient HP1D2 alleles.
The sterile insect technique is protected from evolution of mate discrimination
21768J. J. Bull and R. Gomulkiewicz, PeerJ, 10:e13301. 2022-04-18 07:53:47.
Background The sterile insect technique (SIT) has been used to suppress and even extinguish pest insect populations. The method involves releasing artificially reared insects (usually males) that, when mating with wild individuals, sterilize the broods. If administered on a large enough scale, the sterility can collapse the population. Precedents from other forms of population suppression, especially chemicals, raise the possibility of resistance evolving against the SIT. Here, we consider resistance in the form of evolution of female discrimination to avoid mating with sterile males. Is resistance evolution expected? Methods We offer mathematical models to consider the dynamics of this process. Most of our models assume a constant-release protocol, in which the same density of males is released every generation, regardless of wild male density. A few models instead assume proportional release, in which sterile releases are adjusted to be a constant proportion of wild males. Results We generally find that the evolution of female discrimination, although favored by selection, will often be too slow to halt population collapse when a constant-release implementation of the SIT is applied appropriately and continually. The accelerating efficacy of sterile males in dominating matings as the population collapses works equally against discriminating females as against non-discriminating females, and rare genes for discrimination are too slow to ascend to prevent the loss of females that discriminate. Even when migration from source populations sustains the treated population, continued application of the SIT can prevent evolution of discrimination. However, periodic premature cessation of the SIT does allow discrimination to evolve. Likewise, use of a ‘proportional-release’ protocol is also prone to escape from extinction if discriminating genotypes exist in the population, even if those genotypes are initially rare. Overall, the SIT is robust against the evolution of mate discrimination provided care is taken to avoid some basic pitfalls. The models here provide insight for designing programs to avoid those pitfalls.
Propagation of seminal toxins through binary expression gene drives could suppress populations
21691J. Hurtado, S. Revale and L. M. Matzkin, Scientific Reports, 12:6332. 2022-04-15 08:22:57.
Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this restriction may be relaxed by using a double gene drive design to spread a split binary expression system. One drive carries a dominant lethal/toxic effector alone and the other a transactivator factor, without which the effector will not act. Only after the drives reach sufficiently high frequencies would individuals have the chance to inherit both system components and the effector be expressed. We explore through mathematical modeling the potential of this design to spread dominant lethal/toxic alleles and suppress populations. We show that this system could be implemented to spread engineered seminal proteins designed to kill females, making it highly effective against polyandrous populations.
A homing suppression gene drive with multiplexed gRNAs maintains high drive conversion efficiency and avoids functional resistance alleles
22572E. Yang, M. Metzloff, A. M. Langmuller, X. J. Xu, A. G. Clark, P. W. Messer and J. Champer, G3-Genes Genomes Genetics, 13. 2022-04-08 09:02:04.
Gene drives are engineered alleles that can bias inheritance in their favor, allowing them to spread throughout a population. They could potentially be used to modify or suppress pest populations, such as mosquitoes that spread diseases. CRISPR/Cas9 homing drives, which copy themselves by homology-directed repair in drive/wild-type heterozygotes, are a powerful form of gene drive, but they are vulnerable to resistance alleles that preserve the function of their target gene. Such resistance alleles can prevent successful population suppression. Here, we constructed a homing suppression drive in Drosophila melanogaster that utilized multiplexed gRNAs to inhibit the formation of functional resistance alleles in its female fertility target gene. The selected gRNA target sites were close together, preventing reduction in drive conversion efficiency. The construct reached a moderate equilibrium frequency in cage populations without apparent formation of resistance alleles. However, a moderate fitness cost prevented elimination of the cage population, showing the importance of using highly efficient drives in a suppression strategy, even if resistance can be addressed. Nevertheless, our results experimentally demonstrate the viability of the multiplexed gRNAs strategy in homing suppression gene drives.
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.
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.
Symbionts and gene drive: two strategies to combat vector-borne disease
21029G.-H. Wang, J. Du, C. Y. Chu, M. Madhav, G. L. Hughes and J. Champer, Trends in Genetics, 2022-03-18 07:56:11.
Mosquitoes bring global health problems by transmitting parasites and viruses such as malaria and dengue. Unfortunately, current insecticide-based control strategies are only moderately effective because of high cost and resistance. Thus, scalable, sustainable, and cost-effective strategies are needed for mosquito-borne disease control. Symbiont-based and genome engineering-based approaches provide new tools that show promise for meeting these criteria, enabling modification or suppression approaches. Symbiotic bacteria like Wolbachia are maternally inherited and manipulate mosquito host reproduction to enhance their vertical transmission. Genome engineering-based gene drive methods, in which mosquitoes are genetically altered to spread drive alleles throughout wild populations, are also proving to be a potentially powerful approach in the laboratory. Here, we review the latest developments in both symbionts and gene drive-based methods. We describe some notable similarities, as well as distinctions and obstacles, relating to these promising technologies.
Rescue by gene swamping as a gene drive deployment strategy
20587K. D. Harris and G. Greenbaum, bioRxiv, 2022.03.08.483503. 2022-03-08 11:25:49.
Gene drives are genetic constructs that can spread deleterious alleles with potential application to population suppression of harmful species. Given that a gene drive can potentially spill over to other populations or even other species, control measures and fail-safes strategies must be considered. Gene drives are designed to generate a rapid demographic decline, while at the same time generating a dynamic change in the population’s genetics. Since these evolutionary and demographic processes are linked and are expected to occur at a similar time-scale during gene drive spread, feedback between these processes may significantly affect the outcome of deployment. To study this feedback and to understand how it affects gene drive spillovers, we developed a gene drive model that combines evolutionary and demographic dynamics in a two-population setting. The model demonstrates how feedback between evolutionary and demographic dynamics can generate additional outcomes to those generated by the evolutionary dynamics alone. We identify an outcome of particular interest, where the short-term suppression of the target population is followed by gene swamping and loss of the gene drive. This outcome could be useful for designing gene drive deployments that temporarily suppress the population, but ultimately do not remain in the population. Using our model, we demonstrate the robustness of this outcome to spillover and to the evolution of resistance, and suggest that it could be used as a fail-safe strategy for gene drive deployment.Competing Interest StatementThe authors have declared no competing interest.
Gene drives and population persistence vs elimination: The impact of spatial structure and inbreeding at low density
20529P. J. Beaghton and A. Burt, Theoretical Population Biology, 2022-03-03 08:28:52.
Synthetic gene drive constructs are being developed to control disease vectors, invasive species, and other pest species. In a well-mixed random mating population a sufficiently strong gene drive is expected to eliminate a target population, but it is not clear whether the same is true when spatial processes play a role. In species with an appropriate biology it is possible that drive-induced reductions in density might lead to increased inbreeding, reducing the efficacy of drive, eventually leading to suppression rather than elimination, regardless of how strong the drive is. To investigate this question we analyse a series of explicitly solvable stochastic models considering a range of scenarios for the relative timing of mating, reproduction, and dispersal and analyse the impact of two different types of gene drive, a Driving Y chromosome and a homing construct targeting an essential gene. We find in all cases a sufficiently strong Driving Y will go to fixation and the population will be eliminated, except in the one life history scenario (reproduction and mating in patches followed by dispersal) where low density leads to increased inbreeding, in which case the population persists indefinitely, tending to either a stable equilibrium or a limit cycle. These dynamics arise because Driving Y males have reduced mating success, particularly at low densities, due to having fewer sisters to mate with. Increased inbreeding at low densities can also prevent a homing construct from eliminating a population. For both types of drive, if there is strong inbreeding depression, then the population cannot be rescued by inbreeding and it is eliminated. These results highlight the potentially critical role that low-density-induced inbreeding and inbreeding depression (and, by extension, other sources of Allee effects) can have on the eventual impact of a gene drive on a target population.
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.
A Closing Window of Opportunity for Gene Drive Governance in the United States
20445K. L. Warmbrod, M. Montague and G. K. Gronvall, Health Security, 20:3-5. 2022-02-15 09:35:05.
The COVID-19 pandemic has brought forth a number of biotechnological advances to enhance the public's health: new diagnostic tests, mRNA vaccines, and new antiviral medications. Biotechnology is also being used to address global challenges like climate change, food insecurity, and building the bioeconomy, which directly or indirectly improve public health. Gene drives are one such biotechnology. They are genetically engineered systems that can alter the inheritance patterns in a host species, such as a mosquito, so that a greater percentage of its progeny inherit a specific desired trait. Research and investments in biotechnology have been used to reduce arthropod-borne infectious diseases, such as malaria and Zika, and to manage or eliminate invasive species.2 Funding thus far has been adequate. For example, Target Malaria, a global consortium of researchers developing a gene drive to decrease the burden of malaria, has an average of US$11.5 million per year in funding.3 Although no gene drive has been released into the environment yet, technologies with similar attributes have been released in field trials, notably by Oxitec in Florida
Uniqueness and stability of periodic solutions for an interactive wild and Wolbachia-infected male mosquito model
20438R. Yan and Q. Sun, Journal of Biological Dynamics, 2022-02-15 09:03:48.
We investigate a mosquito population suppression model, which includes the release of Wolbachia-infected males causing incomplete cytoplasmic incompatibility (CI). The model consists of two sub-equations by considering the density-dependent birth rate of wild mosquitoes. By assuming the release waiting period T is larger than the sexual lifespan T¯ of Wolbachia-infected males, we derive four thresholds: the CI intensity threshold sh∗, the release amount thresholds g∗ and c∗, and the waiting period threshold T∗. From a biological view, we assume sh > sh∗ throughout the paper. When g∗ < c < c∗, we prove the origin E0 is locally asymptotically stable iff T < T∗, and the model admits a unique T-periodic solution iff T ≥ T∗, which is globally asymptotically stable. When c ≥ c∗, we show the origin E0 is globally asymptotically stable iff T ≤ T∗, and the model has a unique T-periodic solution iff T > T∗, which is globally asymptotically stable. Our theoretical results are confirmed by numerical simulations.
Monitoring Needs for Gene Drive Mosquito Projects: Lessons From Vector Control Field Trials and Invasive Species
20177G. Rašić, N. F. Lobo, E. H. Jeffrey Gutiérrez, C. H. Sánchez and J. M. Marshall, Frontiers in Genetics, 12:780327. 2022-01-25 09:18:49.
As gene drive mosquito projects advance from contained laboratory testing to semi-field testing and small-scale field trials, there is a need to assess monitoring requirements to: i) assist with the effective introduction of the gene drive system at field sites, and ii) detect unintended spread of gene drive mosquitoes beyond trial sites, or resistance mechanisms and non-functional effector genes that spread within trial and intervention sites. This is of particular importance for non-localized gene drive projects, as the potential scale of intervention means that monitoring is expected to be more costly than research, development and deployment. Regarding monitoring needs for population replacement systems, lessons may be learned from experiences with Wolbachia-infected mosquitoes, and for population suppression systems, from experiences with releases of genetically sterile male mosquitoes. For population suppression systems, assessing monitoring requirements for tracking population size and detecting rare resistant alleles are priorities, while for population replacement systems, allele frequencies must be tracked, and pressing concerns include detection of gene drive alleles with non-functional effector genes, and resistance of pathogens to functional effector genes. For spread to unintended areas, open questions relate to the optimal density and placement of traps and frequency of sampling in order to detect gene drive alleles, drive-resistant alleles or non-functional effector genes while they can still be effectively managed. Invasive species management programs face similar questions, and lessons may be learned from these experiences. We explore these monitoring needs for gene drive mosquito projects progressing through the phases of pre-release, release and post-release.
A gene drive does not spread easily in populations of the honey bee parasite Varroa destructor
20173N. R. Faber, A. B. Meiborg, G. R. McFarlane, G. Gorjanc and B. A. Harpur, Apidologie, 52:1112-1127. 2022-01-25 09:13:37.
Varroa mites (Varroa destructor) are the most significant threat to beekeeping worldwide. They are directly or indirectly responsible for millions of colony losses each year. Beekeepers are somewhat able to control varroa populations through the use of physical and chemical treatments. However, these methods range in effectiveness, can harm honey bees, can be physically demanding on the beekeeper, and do not always provide complete protection from varroa. More importantly, in some populations varroa mites have developed resistance to available acaricides. Overcoming the varroa mite problem will require novel and targeted treatment options. Here, we explore the potential of gene drive technology to control varroa. We show that spreading a neutral gene drive in varroa is possible but requires specific colony-level management practices to overcome the challenges of both inbreeding and haplodiploidy. Furthermore, continued treatment with acaricides is necessary to give a gene drive time to fix in the varroa population. Unfortunately, a gene drive that impacts female or male fertility does not spread in varroa. Therefore, we suggest that the most promising way forward is to use a gene drive which carries a toxin precursor or removes acaricide resistance alleles. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13592-021-00891-5.
Lab-scale characterization and semi-field trials of Wolbachia Strain wAlbB in a Taiwan Wolbachia introgressed Ae. aegypti strain
20383W. L. Liu, H. Y. Yu, Y. X. Chen, B. Y. Chen, S. N. Leaw, C. H. Lin, M. P. Su, L. S. Tsai, Y. Chen, S. H. Shiao, Z. Y. Xi, A. C. C. Jang and C. H. Chen, PLOS Neglected Tropical Diseases, 16:24. 2022-01-11 08:53:33.
Author summaryPrior to open field release, new genetic approaches that interfere with mosquito abilities and reduce mosquito population density require progressive evaluation both in the laboratory and contained field trials. Trials in contained outdoor systems are thus an important step and allow for evaluation of the effectiveness and reliability of Wolbachia-infected Aedes aegypti (wAlbB-Tw) in settings that incorporate natural environmental variations. We describe a semi-field system designed to study the ability of wAlbB-Tw mosquitoes to suppress local mosquito populations. We provide a protocol for establishing, maintaining, and monitoring Ae. aegypti population densities inside field cages. These results pave the way for the open release of wAlbB-Tw-infected Ae. aegypti mosquitoes in the field. Dengue fever is one of the most severe viral diseases transmitted by Aedes mosquitoes, with traditional approaches of disease control proving insufficient to prevent significant disease burden. Release of Wolbachia-transinfected mosquitoes offers a promising alternative control methodologies; Wolbachia-transinfected female Aedes aegypti demonstrate reduced dengue virus transmission, whilst Wolbachia-transinfected males cause zygotic lethality when crossed with uninfected females, providing a method for suppressing mosquito populations. Although highly promising, the delicate nature of population control strategies and differences between local species populations means that controlled releases of Wolbachia-transinfected mosquitoes cannot be performed without extensive testing on specific local Ae. aegypti populations. In order to investigate the potential for using Wolbachia to suppress local Ae. aegypti populations in Taiwan, we performed lab-based and semi-field fitness trials. We first transinfected the Wolbachia strain wAlbB into a local Ae. aegypti population (wAlbB-Tw) and found no significant changes in lifespan, fecundity and fertility when compared to controls. In the laboratory, we found that as the proportion of released male mosquitoes carrying Wolbachia was increased, population suppression could reach up to 100%. Equivalent experiments in semi-field experiments found suppression rates of up to 70%. The release of different ratios of wAlbB-Tw males in the semi-field system provided an estimate of the optimal size of male releases. Our results indicate that wAlbB-Tw has significant potential for use in vector control strategies aimed at Ae. aegypti population suppression in Taiwan. Open field release trials are now necessary to confirm that wAlbB-Tw mediated suppression is feasible in natural environments.
Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse in Drosophila
19441G. Oberhofer, T. Ivy and B. A. Hay, Proceedings of the National Academy of Sciences, 118:e2107413118. 2021-12-01 20:58:01.
One strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise benign virus or chemical, or occur naturally on a seasonal basis, such as a change in temperature. Cleave and Rescue (ClvR) selfish genetic elements use Cas9 and guide RNAs (gRNAs) to disrupt endogenous versions of an essential gene while also including a Rescue version of the essential gene resistant to disruption. ClvR spreads by creating loss-of-function alleles of the essential gene that select against those lacking it, resulting in populations in which the Rescue provides the only source of essential gene function. As a consequence, if function of the Rescue, a kind of Trojan horse now omnipresent in a population, is condition dependent, so too will be the survival of that population. To test this idea, we created a ClvR in Drosophila in which Rescue activity of an essential gene, dribble, requires splicing of a temperature-sensitive intein (TS-ClvRdbe). This element spreads to transgene fixation at 23 °C, but when populations now dependent on Ts-ClvRdbe are shifted to 29 °C, death and sterility result in a rapid population crash. These results show that conditional population elimination can be achieved. A similar logic, in which Rescue activity is conditional, could also be used in homing-based drive and to bring about suppression and/or killing of specific individuals in response to other stimuli.
Propagation of seminal toxins through binary expression gene drives can suppress polyandrous populations
19953J. Hurtado, S. Revale and L. M. Matzkin, bioRxiv, 2021.11.23.469777. 2021-11-24 09:48:59.
Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this restriction may be relaxed by using a double gene drive design to spread a split binary expression system. One drive carries a dominant lethal/toxic effector alone and the other a transactivator factor, without which the effector will not act. Only after the drives reach sufficiently high frequencies would individuals have the chance to inherit both system components and the effector be expressed. We explore through mathematical modeling the potential of this design to spread dominant lethal/toxic alleles and suppress populations. We show that this system could be implemented to spread engineered seminal proteins designed to kill females, making it highly effective against polyandrous populations.Competing Interest StatementThe authors have declared no competing interest.
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.
Malaria modeling and optimal control using sterile insect technique and insecticide-treated net
19230L. Cai, L. Bao, L. Rose, J. Summers and W. Ding, Applicable Analysis, 2021-11-05 21:55:36.
We investigate a malaria transmission model with SEIR (susceptible-exposed-infected-recovered) classes for the human population, SEI (susceptible-exposed-infected) classes for the wild mosquitoes and an additional class for the sterile mosquitoes. The basic reproduction number of the disease transmission is obtained, and a release threshold of the sterile mosquitoes is provided. We formulate an optimal control problem in which the goal is to minimize both the infected human populations and the cost to implement two control strategies: the release of sterile mosquitoes and the usage of insecticide-treated nets to reduce the malaria transmission. Adjoint equations are derived, and the characterization of the optimal controls is established. Finally, we quantify the effectiveness of the two interventions aimed at limiting the spread of malaria transmission. A combination of both strategies leads to more rapid elimination of the wild mosquito population that can suppress malaria transmission. Numerical simulations are provided to illustrate the results.
Will freeing ourselves (forever) from mosquitoes soon be a realizable “dream”? Pros and cons of an epochal turning point – breaking latest news
19160Annonymous, Breaking Latest News, 2021-11-05 14:34:10.
Also true for a dangerous insect like the mosquito: due to the pathologies of which vector, such as the malaria, the dengue o la yellow fever, every year in the world about 800 thousand people die. There are therefore quite a few reasons to want to get rid of it, not just the itchy summer bites, and thanks to the technique developed by Professor Crisanti it would seem possible, in a not too distant future. It starts from a premise: Not that we want to get rid of all mosquitoes. There are around 3,500 species of mosquitoes and fortunately only a few transmit parasitic diseases such as malaria or others that cause diseases such as zika and dengue. So if I want to get rid of malaria I have to attack malaria. Traditionally this has been done with insecticides which have shown all their limits and dangers. These measures, which are apparently simple, require sustainability over time, require resources and political continuity. All this is missing today. Hence biotechnology, the idea of making mosquitoes themselves do this job. If we manage to modify the genetic characteristics of mosquitoes, we can theoretically create mosquitoes that do not reproduce or that do not transmit the infection.
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.
Conditional knockdown of transformer in sheep blow fly suggests a role in repression of dosage compensation and potential for population suppression
19004M. E. Williamson, Y. Yan and M. J. Scott, PLOS Genetics, 17:e1009792. 2021-10-18 15:15:17.
In the fruit fly Drosophila melanogaster and in the mosquito Anopheles gambiae, a single gene (Sxl in D. melanogaster, fle in A. gambiae) controls the development of female-specific tissues and X chromosome dosage compensation, which is the equalization of X-linked gene products in males and females. In this study we find evidence that the transformer gene is essential for somatic sex differentiation and repression of X chromosome dosage compensation in female sheep blow fly, Lucilia cuprina. In several of the transgenic strains developed, females are transformed into males on diet that lacks tetracycline. Consequently, these strains could be part of a genetic control program of this major pest of sheep in Australia.
Gene drive and RNAi technologies: a bio-cultural review of next-generation tools for pest wasp management in New Zealand
19000S. Palmer, P. K. Dearden, O. R. Mercier, A. King-Hunt and P. J. Lester, Journal of the Royal Society of New Zealand, 1-18. 2021-10-14 15:09:43.
There is a global need for novel, next-generation technologies and techniques to manage pest species. We review work on potential step-changing technologies for large landscape (>1000 hectares) pest management of social Vespula wasps. We also review M?ori perspectives on these controls to gauge social and cultural acceptability to research, test and use of novel controls. Approaches discussed are the use of gene silencing (RNAi) and gene drives (CRISPR-Cas 9) involving genetic modification, which has potential for pest control but vary in feasibility, cost, benefits and off-target risks. RNAi may be better suited for wasp control in high-value cropping systems due to scaling inefficiencies. Gene drives offer potential for large-scale control but would require legislative and wide social deliberation due to their status as genetic modification. Both RNAi and gene drives will require consultation with tangata whenua. M?ori interest groups agreed that exotic wasps must be controlled and expressed aversion to non-targeted traditional control methods. We present a diversity of opinions in parallel with scientific research underscoring the need for continued dialogue with M?ori. Novel biotechnological controls must satisfy a broad range of social and cultural criteria, receive regulatory approval, along with being demonstrated as safe, selective, and cost-effective.
Discrete dynamical models on Wolbachia infection frequency in mosquito populations with biased release ratios
18717Y. Shi and B. Zheng, Journal of Biological Dynamics, 2021-09-18 14:11:29.
We develop two discrete models to study how supplemental releases affect the Wolbachia spreading dynamics in cage mosquito populations. The first model focuses on the case when only infected males are released at each generation. This release strategy has been proved to be capable of speeding up the Wolbachia persistence by suppressing the compatible matings between uninfected individuals. The second model targets the case when only infected females are released at each generation. For both models, detailed model formulation, enumeration of the positive equilibria and their stability analysis are provided. Theoretical results show that the two models can generate bistable dynamics when there are three positive equilibrium points, semi-stable dynamics for the case of two positive equilibrium points. And when the positive equilibrium point is unique, it is globally asymptotically stable. Some numerical simulations are offered to get helpful implications on the design of the release strategy.
Novel Sterile Insect Technology Program Results in Suppression of a Field Mosquito Population and Subsequently to Reduced Incidence of Dengue
30892Lisiane de Castro Poncio, Filipe Apolinário dos Anjos, Deborah A de Oliveira, Débora Rebechi, et al., The Journal of Infectious Diseases, 224:1005-1014. 2021-09-15 08:29:17.
There is a steady rise in the global incidence of Aedes-borne arbovirus disease. It has become urgent to develop alternative solutions for mosquito vector control. We developed a new method of sterilization of male mosquitoes with the goal to suppress a local Aedes aegypti population and to prevent the spread of dengue. Sterile male mosquitoes were produced from a locally acquired Ae. aegypti colony by using a treatment that includes double-stranded RNA and thiotepa. A field study was conducted with sterile mosquito releases being performed on a weekly basis in predefined areas. There were 2 intervention periods (INT1 and INT2), with treatment and control areas reversed between INT1 and INT2. During INT1, releases in the treated area resulted in up to 91.4% reduction of live progeny of field Ae. aegypti mosquitoes recorded over time, while the control neighborhoods (no releases of sterile male mosquitoes) remained highly infested. The successful implementations of the program during INT1 and INT2 were associated with 15.9-fold and 13.7-fold lower incidences of dengue in the treated area compared to the control areas, respectively. Our data show the success of this new sterile insect technology-based program in preventing the spread of dengue.
A supernumerary “B-sex” chromosome drives male sex determination in the Pachón cavefish, Astyanax mexicanus
18508B. Imarazene, K. Du, S. Beille, E. Jouanno, R. Feron, Q. Pan, J. Torres-Paz, C. Lopez-Roques, A. Castinel, L. Gil, C. Kuchly, C. Donnadieu, H. Parrinello, L. Journot, C. Cabau, M. Zahm, C. Klopp, T. Pavlica, A. Al-Rikabi, T. Liehr, S. A. Simanovsky, J. Bo, Current Biology, 2021-09-09 14:28:39.
Sex chromosomes are generally derived from a pair of classical type-A chromosomes, and relatively few alternative models have been proposed up to now.(1)(,)(2) B chromosomes (Bs) are supernumerary and dispensable chromosomes with non-Mendelian inheritance found in many plant and animal species(3)(,)(4) that have often been considered as selfish genetic elements that behave as genome parasites.(5)(,)(6) The observation that in some species Bs can be either restricted or predominant in one sex(7-14) raised the interesting hypothesis that Bs could play a role in sex determination.(15) The characterization of putative B master sex-determining (MSD) genes, however, has not yet been provided to support this hypothesis. Here, in Astyanax mexicanus cavefish originating from Pachón cave, we show that Bs are strongly male predominant. Based on a high-quality genome assembly of a B-carrying male, we characterized the Pachón cavefish B sequence and found that it contains two duplicated loci of the putative MSD gene growth differentiation factor 6b (gdf6b). Supporting its role as an MSD gene, we found that the Pachón cavefish gdf6b gene is expressed specifically in differentiating male gonads, and that its knockout induces male-to-female sex reversal in B-carrying males. This demonstrates that gdf6b is necessary for triggering male sex determination in Pachón cavefish. Altogether these results bring multiple and independent lines of evidence supporting the conclusion that the Pachón cavefish B is a "B-sex" chromosome that contains duplicated copies of the gdf6b gene, which can promote male sex determination in this species.
Gene drive escape from resistance depends on mechanism and ecology
18261F. Cook, J. J. Bull and R. Gomulkiewicz, bioRxiv, 2021.08.30.458221. 2021-08-31 13:20:26.
Gene drives can potentially be used to suppress pest populations, and the advent of CRISPR technology has made it feasible to engineer them in many species, especially insects. What remains largely unknown for implementations is whether anti-drive resistance will evolve to block the population suppression. An especially serious threat to some kinds of drive is mutations in the CRISPR cleavage sequence that block the action of CRISPR, but designs have been proposed to avoid this type of resistance. Various types of resistance at loci away from the cleavage site remain a possibility, which is the focus here. It is known that modest-effect suppression drives can essentially `outrun' unlinked resistance even when that resistance is present from the start. We demonstrate here how the risk of evolving (unlinked) resistance can be further reduced without compromising overall suppression by introducing multiple suppression drives or by designing drives with specific ecological effects. However, we show that even modest-effect suppression drives remain vulnerable to the evolution of extreme levels of inbreeding, which halt the spread of the drive without actually interfering with its mechanism. The landscape of resistance evolution against suppression drives is therefore complex, but avenues exist for enhancing gene drive success.Competing Interest StatementThe authors have declared no competing interest.
Gene drives gaining speed
17972E. Bier, Nature Reviews Genetics, 2021-08-06 13:50:56.
Gene drives are selfish genetic elements that are transmitted to progeny at super-Mendelian (>50%) frequencies. Recently developed CRISPR–Cas9-based gene-drive systems are highly efficient in laboratory settings, offering the potential to reduce the prevalence of vector-borne diseases, crop pests and non-native invasive species. However, concerns have been raised regarding the potential unintended impacts of gene-drive systems. This Review summarizes the phenomenal progress in this field, focusing on optimal design features for full-drive elements (drives with linked Cas9 and guide RNA components) that either suppress target mosquito populations or modify them to prevent pathogen transmission, allelic drives for updating genetic elements, mitigating strategies including trans-complementing split-drives and genetic neutralizing elements, and the adaptation of drive technology to other organisms. These scientific advances, combined with ethical and social considerations, will facilitate the transparent and responsible advancement of these technologies towards field implementation.
Host-associated differentiation of target pests should be assessed before using gene drive as a pest control tool – an opinion
17955R. F. Medina, Entomologia Experimentalis et Applicata, 2021-08-01 12:42:29.
Abstract Advances in gene editing have made feasible the potential use of gene drive for pest control. Ecological risk assessments will certainly be required before this technology can be released into open fields. In this article I argue for the importance to include host-associated differentiation (HAD) as part of ecological risk assessment models due to its potential to modulate gene drive spread and risk. Depending on context, HAD may hamper or facilitate pest control efforts using gene drives. Overlooking HAD may impair pest suppression goals and inflate estimations of effective population sizes whereas its inclusion within gene drive deployment strategies, as a form of ecological containment, may facilitate gene drive implementation under specific scenarios. Because HAD varies geographically and among closely related species, it will need to be assessed on a case-by-case basis. Failure to incorporate HAD within ecological risk assessment models may undermine pest control goals and diminish the accuracy of estimated ecological risks associated with gene drive releases.
Scientists eradicate malaria-transmitting mosquitos using genetic engineering which make females infertile in new study which takes one step closer to wiping out the disease worldwide.
18078C. Ciaccia, Daily Mail, 2021-07-30 17:09:51.
Malaria kills nearly 500,000 people globally every year, but scientists have now figured out a way to use CRISPR gene-editing technology to make female mosquitoes infertile, described as a 'game-changer' for ending the deadly disease. Researchers from Imperial College London, Genomics Genetics and Biology, and the Liverpool School of Tropical Medicine were able to use a gene drive for the first time to not only show that blocking female reproduction worked in a lab setting, but natural-like setting as well. The researchers targeted the mosquito species Anopheles gambiae, which is responsible for the majority of malaria transmissions in sub-Saharan Africa. The gene-drives targets the gene known as 'doublesex' in these mosquitoes.
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.
Transgenic expression of Nix converts genetic females into males and allows automated sex sorting in Aedes albopictus
17888C. Lutrat, R. P. Olmo, T. Baldet, J. Bouyer and E. Marois, bioRxiv, 2021.07.28.454191. 2021-07-29 12:43:42.
Aedes albopictus is a major vector of arboviruses. Better understanding of its sex determination is crucial for developing mosquito control tools, especially genetic sexing strains. In Aedes aegypti, Nix is the primary gene responsible for masculinization and Nix-expressing genetic females develop into fertile, albeit flightless, males. In Ae. albopictus, Nix has also been implicated in masculinization but its role remains to be further characterized. In this work, we established Ae. albopictus transgenic lines ectopically expressing Nix. Several were composed exclusively of genetic females, with transgenic individuals being phenotypic and functional males due to the expression of the Nix transgene. Their reproductive fitness was marginally impaired, while their flight performance was similar to controls. Overall, our results show that Nix is sufficient for full masculinization in Ae. albopictus. Moreover, the transgene construct contains a fluorescence marker allowing efficient automated sex sorting. Consequently, such strains constitute valuable sexing strains for genetic control.Competing Interest StatementThe authors have declared no competing interest.
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.
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.
The Aedes aegypti (Diptera: Culicidae) hsp83 Gene Promoter Drives Strong Ubiquitous DsRed and ZsGreen Marker Expression in Transgenic Mosquitoes
18145S. H. Webster and M. J. Scott, Journal of Medical Entomology, 2021-07-24 17:29:43.
Transgenic strains of the mosquito disease vector Aedes aegypti (L.) are being developed for population suppression or modification. Transgenic mosquitoes are identified using fluorescent protein genes. Here we describe DsRed and ZsGreen marker genes driven by the constitutive Ae. aegypti heat shock protein 83 (hsp83) promoter in transgenic mosquitoes. Transgenic larvae and pupae show strong full body expression of the red and green fluorescent proteins. This greatly assists in screening for transgenic individuals while making new or maintaining already established lines. Transient marker gene expression after embryo microinjection was readily visible in developing larvae allowing the separation of individuals that are more likely to produce transgenic offspring. The strongly expressed marker genes developed in this study should facilitate the detection of transgenic Ae. aegypti larvae or pupae in the field.
Combating mosquito-borne diseases using genetic control technologies
17735G.-H. Wang, S. Gamez, R. R. Raban, J. M. Marshall, L. Alphey, M. Li, J. L. Rasgon and O. S. Akbari, Nature Communications, 12:4388. 2021-07-19 13:06:45.
Mosquito-borne diseases, such as dengue and malaria, pose significant global health burdens. Unfortunately, current control methods based on insecticides and environmental maintenance have fallen short of eliminating the disease burden. Scalable, deployable, genetic-based solutions are sought to reduce the transmission risk of these diseases. Pathogen-blocking Wolbachia bacteria, or genome engineering-based mosquito control strategies including gene drives have been developed to address these problems, both requiring the release of modified mosquitoes into the environment. Here, we review the latest developments, notable similarities, and critical distinctions between these promising technologies and discuss their future applications for mosquito-borne disease control.
Gene drive that results in addiction to a temperature sensitive version of an essential gene triggers population collapse in Drosophila
17609G. Oberhofer, B. Hay and T. Ivy, bioRxiv, 2021.07.03.451005. 2021-07-04 14:38:01.
One strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise benign virus or chemical, or occur naturally on a seasonal basis, such as a change in temperature. Cleave and Rescue (ClvR) selfish genetic elements use Cas9 and gRNAs to disrupt endogenous versions of an essential gene, while also including a Rescue version of the essential gene resistant to disruption. ClvR spreads by creating loss-of-function alleles of the essential gene that select against those lacking it, resulting in populations in which the Rescue provides the only source of essential gene function. In consequence, if function of the Rescue, a kind of Trojan horse now omnipresent in a population, is condition-dependent, so too will be the survival of that population. To test this idea we created a ClvR in Drosophila in which Rescue activity of an essential gene, dribble, requires splicing of a temperature-sensitive intein (TS-ClvRdbe). This element spreads to transgene fixation at 23° C, but when populations now dependent on TS-ClvRdbe are shifted to 29° C death and sterility result in a rapid population crash. These results show that conditional population elimination can be achieved. A similar logic, in which Rescue activity is conditional, could also be used in HEG-based drive, and to bring about suppression and/or killing of specific individuals in response to other stimuli.Competing Interest StatementThe authors have filed patent applications on ClvR and related 336 technologies (U.S. Application No. 15/970,728 and No. 16/673,823 ; provisional patent No. 337 CIT-8511-P )
Wolbachia-mediated sterility suppresses Aedes aegypti populations in the urban tropics
19443Project Wolbachia-Singapore Consortium, medRxiv, 2021-06-17 21:07:26.
Incompatible insect technique (IIT) via releases of male Wolbachiainfected mosquitoes is a promising tool for dengue control. In a three-year trial in Singaporean high-rise housing estates, we demonstrated that Wolbachia-based IIT dramatically reduces both wildtype Aedes aegypti populations [reductions of 92.7% (95% CI: 84.7%–95.8%) and 98.3% (97.7%–99.8%)] and dengue incidence [reductions of 71% (43%-87%) to 88% (57%-99%)] in the targeted areas. The study highlights the need to ensure adequate vertical distribution of released males in high-rise buildings, address immigration of wildtype females from neighboring areas, and prevent and mitigate stable establishment of Wolbachia in field mosquito populations. Our results demonstrate the potential of Wolbachia-based IIT (supplemented with irradiation, in Singapore’s context) for strengthening dengue control in tropical cities, where dengue burden is the greatest.
Area-Wide Integrated Management of a Glossina palpalis gambiensis Population from the Niayes Area Of Senegal: A review of operational research in support of a phased conditional approach
25657M. J. B. Vreysen, M. T. Seck, B. Sall, A. G. Mbaye, M. Bassene, A. G. Fall, M. Lo and J. Bouyer, AREA-WIDE INTEGRATED PEST MANAGEMENT:, 2021-06-12 13:45:08.
In 2005, the Government of Senegal initiated a project entitled "Projet de lutte contre les glossines dans les Niayes" (Tsetse control project in the Niayes) with the aim of creating a zone free of Glossina palpalis gambiensis in that area. The project received technical and financial support from the International Atomic Energy Agency (IAEA), the Food and Agriculture Organization of the United Nations (FAO), the Centre de Cooperation Internationale en Recherche Agronomique pour le Developpement (CIRAD) and the US Department of State through the Peaceful Uses Initiative (PUI). It was implemented in the context of the Pan African Tsetse and Trypanosomosis Eradication Campaign (PATTEC) following a phased conditional approach (PCA) that entails implementation in distinct phases, in which support to the next phase is conditional upon completion of all (or at least the majority of) activities in the previous phase. In the case of the tsetse project in Senegal, the PCA consisted of 4 phases: (1) commitment of all stakeholders and training, (2) baseline data collection, feasibility studies and strategy development, (3) preparatory pre-operational activities and (4) operational activities. This paper provides an overview of the main activities that were carried out within each phase, with emphasis on the operational research carried out in phases 2 and 3, that was instrumental in guiding the project's decision-making. Activities of phase 2 focused on the collection of entomological, veterinary, socio-economic and environmental baseline data, and a population genetics study that proved the isolated character of the G. p. gambiensis population of the Niayes. These data enabled the tsetse-infested area to be delimited to 1000 km(2), the impact of animal trypanosomosis on the farmers' welfare to be quantified (annual benefits of 2 million Euro in the tsetse-infested zone), and the formulation of an area-wide integrated pest management (AW-IPM) strategy that included a sterile insect (SIT) component to eradicate the isolated tsetse populations from the Niayes. In view of the extreme fragmentation of the remaining favourable habitat of the Niayes and the high human population density (peri-urban area), which excluded the possibility of using the Sequential Aerosol Technique, the IPM strategy that was selected comprised the suppression of the tsetse population with insecticide-impregnated traps/targets and the use of "pour-on" for cattle, followed by the release of sterile males to eliminate the remaining relic pockets. During phase 3, the pre-operational phase, a series of activities were carried out that were needed to implement the operational phase. These included the establishment of a colony of tsetse originating from the target area in Senegal, competitiveness studies between the sterile flies and those from the target area, development of transport methods for long-distance shipments of sterile male pupae, competitiveness of the sterile male flies after release in the target area, development of aerial release methods (including a new chilled adult release system) and development of a Maxent-based distribution model to guide the suppression, sterile male releases and monitoring of the eradication campaign. To be able to properly manage the eradication campaign in different phases, the entire target area was divided into 3 operational blocks. This paper demonstrates how, during the operational phase, scientific principles continued to guide the implementation process. The results to date are encouraging, i.e. the deployment of 269 insecticide-impregnated Vavoua traps in favourable habitat of Block 1 reduced the apparent density of the G. p. gambiensis population significantly (from 0.42 (SD 0.39) to 0.04 (SD 0.11) flies/trap/day). This was followed by the aerial release of sterile males that reduced the apparent density to zero after six months of releases. The last wild fly was trapped on August 9, 2012 in Block 1. In Block 2, during the suppression, the apparent fly density dropped from 1.24 (SD 1.23) to 0.005 (SD 0.017) flies/trap/day. Sterile male releases were initiated in February 2014 and expanded to cover the entire Block 2 in January 2015. The apparent fly density has so far been reduced to < 0.001 fly per trap per day until the end of 2018 and releases are still ongoing. The results of the campaign are discussed with respect to the "adaptive management approach" used, which was deemed critical for the success of the campaign.
New biocontrol research to help prevent mice plagues
17206Anonymous, The National Tribune, 2021-06-04 15:41:51.
Scientists at the University of Adelaide are partnering with the CSIRO and the Centre for Invasive Species Solutions on breakthrough genetic biocontrol research to help control mice populations and prevent future mice plagues. The three-year research program will identify fast acting gene drives, which are designed to spread an inherited characteristic for population control through mice populations at higher-than-normal rates. This would effectively enable scientists to interrupt the breeding cycle and keep mice populations at manageable levels. The NSW Government will provide $1.8 million towards the project to fast-track the delivery of the ‘gene drive technology’ as part of a range of measures not only to mitigate the impacts of the mice currently across NSW, but also to create options to reduce the impact of future population spikes.
Experimental demonstration of tethered gene drive systems for confined population modification or suppression
17153M. Metzloff, E. Yang, S. Dhole, A. G. Clark, P. W. Messer and J. Champer, bioRxiv, 2021.05.29.446308. 2021-05-30 10:50:23.
Tethered drive systems, in which a locally confined gene drive provides the CRISPR nuclease needed for a homing drive, could provide a solution to this problem, offering the power of a homing drive and confinement of the supporting drive. Here, we demonstrate the engineering of a tethered drive system in Drosophila, using a TARE drive to support modification and suppression homing drives. Each drive was able to bias inheritance in its favor, and the TARE drive was shown to spread only when released above a threshold frequency in experimental cage populations. After the TARE drive had established in the population, it facilitated the spread of a subsequently released split homing modification drive (to all individuals in the cage) and of a homing suppression drive (to its equilibrium frequency). Our results show that the tethered drive strategy is a viable and easily engineered option for providing confinement of homing drives to target populations. Competing Interest StatementThe authors have declared no competing interest.
Scientists want to alter rodent genes to prevent mice plagues
17092P. Hannon, The Sydney Morning Herald, 2021-05-23 10:52:32.
Mice plagues, such as the one ravaging parts of inland NSW, could become a thing of the past if scientists succeed in modifying the genes of the rodents so that populations crash before they can take off. Paul Thomas, a researcher at the University of Adelaide, is part of an international consortium including the CSIRO and the US Department of Agriculture, studying how to safely alter genes to make female mice infertile. The techniques learned could potentially be applied to other damaging invasive mammals such as cats and foxes.
Modeling and analysis of the implementation of the Wolbachia incompatible and sterile insect technique for mosquito population suppression.
17098B. Zheng, J. S. Yu and J. Li, Siam Journal on Applied Mathematics, 81:718-740. 2021-04-29 13:06:06.
Mathematical analysis may offer guidance in designing effective mass release strategies for the area-wide application of this Wolbachia incompatible and sterile insect technique in the future. The two most crucial concerns in designing release strategies are how often and in what amount should Wolbachia-infected mosquitoes be released in order to guarantee population suppression. Motivated by the experimental data from the Guangzhou mosquito factory and the release strategy implemented on two islands, we formulate and analyze a mosquito population suppression model considering the situation for the release period T less than the sexual lifespan of Wolbachia-infected males. We define release amount thresholds g(1)* and g(2)* with g(1)* < g(2)*. When the release amount c satisfies c >= g(2)*, population suppression is always achievable, as is mathematically manifested by the global asymptotic stability of the origin. However, when c is an element of (0, g(1)*], we find that suppression can be achieved only if the initial wild mosquito population is small enough. This is mathematically proved by the local asymptotic stability of the origin, together with the existence of exactly two T-periodic solutions, one of which is asymptotically stable and the other of which is unstable, with T being the waiting period between two consecutive releases. For c is an element of (g(1)*, g(2)*), we find sufficient conditions on the nonexistence of T-periodic solution, and the existence of at most two T-periodic solutions.
Village hears from experts as genetic-mosquito release experiment nears.
16678J. McCarthy, KEYSWEEKLY, 2021-03-26 14:56:47.
On March 18, Islamorada Village Council heard from several independent scientists who discussed information and issues behind the genetically modified mosquitoes for population and disease suppression. The scientists collectively said they’re neither for nor against the release. A representative from the Florida Keys Mosquito Control District and one from Oxitec responded following the presentation. Fred Gould, professor of North Carolina State’s Department of Entomology and Plant Pathology, briefly explained the strain of mosquitoes (OX5034) set for release. He said he was involved with another strain of genetically modified mosquitoes in development in 2010 when a field case study was conducted in Mexico. “In the laboratory, it turned out the male mosquitoes flew fine and mated well. But in the real environment, they weren’t as strong as the wild type mosquitoes and they basically had 3% of the matings. Instead of having half the matings, they had very few,” he said. Gould went on to say that this is also shown in work by Oxitec in Brazil, where it turns out that the genetic mosquitoes “are not very fit.” “It would take 30 of them, at least, to be equal to an individual wild type in terms of how many matings you have,” he said. “When you’re thinking about that, you have to recognize you have to release a lot of mosquitoes in order to have any activity. I just want to bring that home to you that it goes up and down as to what that percent fitness is, and we don’t know what that’ll look like in Florida. “Will it work? I want to say it might work just fine,” he continued. “There’s a chance that they’ll be doing these releases and it won’t be a simple thing.”
The ethical scientist in a time of uncertainty
16620L. Zoloth, Cell, 184:1430-1439. 2021-03-18 17:59:56.
Using the example of gene drives for malaria control to explore the problem of deep uncertainty in biomedical research, I argue that profound uncertainty is an essential feature. Applying the language and presumptions of the discipline of philosophical ethics, I describe three types of uncertainty that raise ethical challenges in scientific research. Rather than mitigate these challenges with excessive precautions and limits on progress, I suggest that researchers can cultivate classic values of veracity, courage, humility, and fidelity in their research allowing science to proceed ethically under conditions of deep uncertainty.
Ultra-conserved sequences in the genomes of highly diverse Anopheles mosquitoes, with implications for malaria vector control
16629S. M. O'Loughlin, A. J. Forster, S. Fuchs, T. Dottorini, T. Nolan, A. Crisanti and A. Burt, G3-Genes Genomes Genetics, 2021-03-18 14:15:51.
Here we search for conserved sequences of 18bp and over in an alignment of 21 Anopheles genomes, spanning an evolutionary timescale of 100 million years, and characterise the resulting sequences according to their location and function. Over 8000 ultra-conserved elements were found across the alignment, with a maximum length of 164 bp. Length-corrected gene ontology analysis revealed that genes containing Anopheles ultra-conserved elements were over-represented in categories with structural or nucleotide binding functions. Known insect transcription factor binding sites were found in 48% of intergenic Anopheles ultra-conserved elements. When we looked at the genome sequences of 1142 wild-caught mosquitoes we found that 15% of the Anopheles ultra-conserved elements contained no polymorphisms. Our list of Anopheles ultra-conserved elements should provide a valuable starting point for the selection and testing of new targets for gene-drive modification in the mosquitoes that transmit malaria.
Meiotic Cas9 expression mediates genotype conversion in the male and female mouse germline.
16618A. J. Weitzel, H. A. Grunwald, R. Levina, V. M. Gantz, S. M. Hedrick, E. Bier and K. L. Cooper, 2021.03.16.435716, 2021-03-17 17:52:21.
We previously showed that such a system of genotype conversion from heterozygous to homozygous after a sequence targeted CRISPR/Cas9 double strand DNA break is feasible in the female mouse germline. In the male germline, however, all double strand breaks were instead repaired by end joining mechanisms to form an 'insertion/deletion' (indel) mutation. These observations suggested that timing Cas9 expression to coincide with meiosis I is critical to favor conditions when homologous chromosomes are aligned and interchromosomal homology directed repair (HDR) mechanisms predominate. Here, using a Cas9 knock-in allele at the Spo11 locus, we show that meiotic expression of Cas9 does indeed mediate genotype conversion in the male as well as in the female germline. However, the low frequency of both HDR and indel mutation in both male and female germlines suggests that Cas9 may be expressed from the Spo11 locus at levels too low for efficient double strand DNA break formation. We suggest that more robust Cas9 expression initiated during early meiosis I may improve the efficiency of genotype conversion and further increase the rate of 'super-Mendelian' inheritance from both male and female mice.Competing Interest StatementVMG, SMH, EB, and KLC hold advisory board positions with Synbal, Inc. All other authors declare that they have no competing interests.
Mosquito anxiety prompts query from congressman
16592T. Java, Keynews.com, 2021-03-10 20:09:26.
Anxiety among some residents over the pending release of hundreds of millions of genetically modified mosquitoes next month in undisclosed locations throughout the Florida Keys has prompted Congressman Carlos Gimenez to seek answers from the U.S. Environmental Protection Agency. The Florida Keys Mosquito Control District and Oxitec, a British-based biotech company, plan to release genetically modified Aedes aegypti mosquitoes in selected neighborhoods between mile markers 10 and 93 as a way to control the wild population of the disease-carrying pest. This is the first experiment of its kind in the U.S.
femaleless Controls Sex Determination and Dosage Compensation Pathways in Females of Anopheles Mosquitoes
16910E. Krzywinska, L. Ferretti, J. Li, J.-C. Li, C.-H. Chen and J. Krzywinski, Current Biology, 31:1084-1091.e4. 2021-03-08 18:07:47.
Here we show that in the African malaria mosquito Anopheles gambiae, a gene, which likely arose in the Anopheles lineage and which we call femaleless (fle), controls sex determination in females by regulating splicing of dsx and fruitless (fru; another terminal gene within a branch of the sex determination pathway). Moreover, fle represents a novel molecular link between the sex determination and dosage compensation pathways. It is necessary to suppress activation of dosage compensation in females, as demonstrated by the significant upregulation of the female X chromosome genes and a correlated female-specific lethality, but no negative effect on males, in response to fle knockdown. This unexpected property, combined with a high level of conservation in sequence and function in anopheline mosquitoes, makes fle an excellent target for genetic control of all major vectors of human malaria.
Sex Determination and Dosage Compensation: femaleless Is the Link in Anopheles Mosquitoes
16908M. Scott, Current Biology, 31:R260-R263. 2021-03-08 18:03:44.
A new study finds that the femaleless gene is essential for sexual development and repression of X-chromosome dosage compensation in the malaria vector Anopheles gambiae. This could provide the basis for a new genetic approach to control this pest.
In Uganda, genetically modified mosquitoes bring hope and fear
16550Anonymous, africanews, 2021-03-05 19:32:29.
Scientists here are investigating whether populations of the malaria-carrying insects can be reduced by genetic modification. They're looking at the viability of releasing large numbers of genetically modified mosquitos into the wild to influence future generations. The study is being led by scientists here at the institute in Kampala with researchers from the Target Malaria group. Dr. Jonathan Kayondo is the principal investigator managing the project. He says the disease can be deadly for children, especially those under five-years-old. "The aim here is to develop a new vector control tool for the suppression of malaria transmission," says Dr. Jonathan Kayondo.
Genetically modified mosquitoes for better health
16527D. Devis, COSMOS, 2021-03-04 18:24:41.
One method of preventing these mosquito-born diseases is to use insecticides to kill the mozzies and remove them, but sometimes this only works as a short term solution, or has unintended devasting effects on the ecosystem. Another method for decreasing the number of disease-carrying mozzies is to introduce disease resistant, genetically modified mozzies. These transgenic mozzies could be part of a gene drive system where they have a newly introduced disease-resistant gene, linked up with CRISPR mechanisms that help the gene dominate in the population by continuing to copy itself through the genome. All of this requires very thorough risk assessment.
Tensions rise as GM mosquito release nears in Florida Keys
16520T. O'Hara, Keynews.com, 2021-03-03 20:29:44.
Tensions seem to be rising as a planned release of genetically modified mosquitoes nears. The British-based biotech company Oxitec plans to release genetically modified Aedes aegypti mosquitoes in the Florida Keys sometime after April, but has yet to disclose exact locations in the Keys or a date.
Quantifying the risk of vector-borne disease transmission attributable to genetically modified vectors
16530G. R. Hosack, A. Ickowicz and K. R. Hayes, Royal Society Open Science, 8:201525. 2021-03-03 18:28:51.
The relative risk of disease transmission caused by the potential release of transgenic vectors, such as through sterile insect technique or gene drive systems, is assessed with comparison with wild-type vectors. The probabilistic risk framework is demonstrated with an assessment of the relative risk of lymphatic filariasis, malaria and o'nyong'nyong arbovirus transmission by mosquito vectors to human hosts given a released transgenic strain of Anopheles coluzzii carrying a dominant sterile male gene construct. Harm is quantified by a logarithmic loss function that depends on the causal risk ratio, which is a quotient of basic reproduction numbers derived from mathematical models of disease transmission. The basic reproduction numbers are predicted to depend on the number of generations in an insectary colony and the number of backcrosses between the transgenic and wild-type lineages. Analogous causal risk ratios for short-term exposure to a single cohort release are also derived. These causal risk ratios were parametrized by probabilistic elicitations, and updated with experimental data for adult vector mortality. For the wild-type, high numbers of insectary generations were predicted to reduce the number of infectious human cases compared with uncolonized wild-type. Transgenic strains were predicted to produce fewer infectious cases compared with the uncolonized wild-type.
Florida Keys moves forward with genetically modified mosquitoes
16524H. Vela, local10.com, 2021-03-03 18:08:13.
The feared GMO mosquitoes are not going away. Opponents of the technology fear the date of the release in the Florida Keys is getting closer, and they are not ready for the possible repercussions of the experiment. The fight over whether or not to release genetically modified mosquitoes in Monroe County has been going on for almost a decade. Barry Wray said the mosquito control team’s contractor wants to deliver the first batch in April. Wray, the executive director of the Florida Keys Environmental Coalition, said he doesn’t believe there is enough evidence to prove that the technology is safe. He said there is a need for independent scientific investigation. “You don’t really know what the long-term outcomes could be or how to quantify those risks, and if you can’t do that scientifically, then you don’t know how to responsibly mitigate it or detect if something is going awry,” Wray said.
When and where will millions of mosquitoes be released? Here are details for Florida Keys
16485D. Goodhue, Miami Herald, 2021-02-25 21:09:17.
The Florida Keys Mosquito Control District announced this week a wide and vague planned range of deployment for the lab-designed mosquitoes — neighborhoods from mile marker 10 to 93. The trial is being conducted by British biotech company Oxitec. It’s a method approved by the U.S. Environmental Protection Agency, the state of Florida, and the mosquito control district’s five-member board, to try to eradicate or significantly reduce the local population of Aedes aegypti mosquitoes.
Mosquito trial will begin in April, but Keys locations won’t be disclosed
16483S. Matthis, KEYSWEEKLY, 2021-02-23 20:54:42.
FKMCD spokesman Chad Huff wrote in an email, “The physical location of each box is still being finalized. Since most will be situated on private property at owner request, FKMCD-Oxitec will NOT be providing specific addresses due to privacy concerns and protection of project integrity.” Phil Goodman, chairman of the FKMCD said the decision to keep addresses confidential was an operations decision, not a decision by the elected board. “Right now, we don’t have any specific sites that are 100 percent selected,” said Andrea Leal, executive director of the FKMCD. “We are just narrowing down areas with potential.”
Modeling impact and cost-effectiveness of gene drives for malaria elimination in the Democratic Republic of the Congo
16477N. Metchanun, C. Borgemeister, G. Amzati, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin, medRxiv, 2020.06.29.20142760. 2021-02-22 13:51:04.
Using a spatially explicit, agent-based model of malaria transmission in eight representative provinces of 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-shredding 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.
Oxitec gears up for test releases
16386T. O'Hara, Keynews.com, 2021-02-10 15:10:19.
The United Kingdom-based biotech company Oxitec will soon announce the test locations and timetable for releasing its genetically modified mosquitoes in the Florida Keys.
Demographic feedbacks can hamper the spatial spread of a gene drive
16203L. Girardin and F. Débarre, arXiv, 2021-01-27 15:32:53.
Our results indicate that taking into account the interplay between population dynamics and population genetics might actually be crucial, as it can effectively reverse the direction of the invasion and lead to failure. Our findings can be extended to other bistable systems, such as the spread of cytoplasmic incompatibilities caused by Wolbachia.
Exploring Gene Drive Technologies in Agriculture, Biodiversity and Human Disease
15963The GBIRd Partnership and The GeneConvene Global Collaborative, Gene Drive Research Forum, 2021-01-14 21:37:12.
The GBIRd Partnership and The GeneConvene Global Collaborative recently collaborated through The Gene Drive Research Forum, to create and produce an engaging conversation between Drs. Fred Gould and Charles Godfray about gene drive technologies – the potential benefits and complicating factors for agriculture, biodiversity, and human disease.
CRISPR and the splice to survive: New gene-editing technology could be used to save species from extinction—or to eliminate them.
16011E. Kolbert, New Yorker, 2021-01-11 14:25:59.
About a year ago, not long before the pandemic began, I paid a visit to the center, which is an hour southwest of Melbourne. The draw was an experiment on a species of giant toad known familiarly as the cane toad. The toad was introduced to Australia as an agent of pest control, but it promptly got out of control itself, producing an ecological disaster. Researchers at the A.C.D.P. were hoping to put the toad back in the bottle, as it were, using crispr.
Double drives and private alleles for localised population genetic control
15945K. Willis and A. Burt, bioRxiv, 2021.01.08.425856. 2021-01-09 16:30:16.
In this paper we propose and model a series of low threshold double drive designs for population suppression, each consisting of two constructs, one imposing a reproductive load on the population and the other inserted into a differentiated locus and controlling the drive of the first. Simple deterministic, discrete-generation computer simulations are used to assess the alternative designs. We find that the simplest double drive designs are significantly more robust to pre-existing cleavage resistance at the differentiated locus than single drive designs, and that more complex designs incorporating sex ratio distortion can be more efficient still, even allowing for successful control when the differentiated locus is neutral and there is up to 50% pre-existing resistance in the target population. Similar designs can also be used for population replacement, with similar benefits. A population genomic analysis of PAM sites in island and mainland populations of the malaria mosquito Anopheles gambiae indicates that the differentiation needed for our methods to work can exist in nature. Double drives should be considered when efficient but localised population genetic control is needed and there is some genetic differentiation between target and non-target populations.
Next-generation tools to control biting midge populations and reduce pathogen transmission
15940P. Shults, L. W. Cohnstaedt, Z. N. Adelman and C. Brelsfoard, Parasites and Vectors, 14:31. 2021-01-07 14:52:23.
Biting midges of the genus Culicoides transmit disease-causing agents resulting in a significant economic impact on livestock industries in many parts of the world. Localized control efforts, such as removal of larval habitat or pesticide application, can be logistically difficult, expensive and ineffective if not instituted and maintained properly. With these limitations, a population-level approach to the management of Culicoides midges should be investigated as a means to replace or supplement existing control strategies. Next-generation control methods such as Wolbachia- and genetic-based population suppression and replacement are being investigated in several vector species. Here we assess the feasibility and applicability of these approaches for use against biting midges. We also discuss the technical and logistical hurdles needing to be addressed for each method to be successful, as well as emphasize the importance of addressing community engagement and involving stakeholders in the investigation and development of these approaches.
Mosquito Sexual Selection and Reproductive Control Programs
15921L. J. Cator, C. A. S. Wyer and L. C. Harrington, Trends in Parasitology, 2021-01-06 18:45:40.
Recent work has generated many key insights about specific aspects of mating behavior and physiology. Here, we synthesize these findings and classify swarming mosquito systems as polygynous. Male mating success is highly variable in swarms and evidence suggests that it is likely determined by both scramble competition between males and female choice. Incorporating this new understanding will improve both implementation and long-term stability of reproductive control tools.
Control of malaria-transmitting mosquitoes using gene drives
15693T. Nolan, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190803. 2020-12-28 15:31:23.
In this article, I will discuss the relative merits of this type of gene drive, as well as barriers to its technical development and to its deployment in the field as malaria control. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'.
Evading resistance to gene drives
15422R. Gomulkiewicz, M. L. Thies and J. J. Bull, bioRxiv, 2020.08.27.270611. 2020-12-12 15:44:15.
Our analyses suggest that among gene drives that cause moderate suppression, toxin-antidote systems are less apt to select for resistance than homing drives. Single drives of moderate effect might cause only moderate population suppression, but multiple drives (perhaps delivered sequentially) would allow arbitrary levels of suppression. The most favorable case for evolution of resistance appears to be with suppression homing drives in which resistance is dominant and fully suppresses transmission distortion; partial suppression by resistance heterozygotes or recessive resistance are less prone to resistance evolution. Given that it is now possible to engineer CRISPR-based gene drives capable of circumventing allelic resistance, this design may allow for the engineering of suppression gene drives that are effectively resistance-proof.
Targeting female flight for genetic control of mosquitoes
15310D. Navarro-Payá, I. Flis, M. A. E. Anderson, P. Hawes, M. Li, O. S. Akbari, S. Basu and L. Alphey, PLOS Neglected Tropical Diseases, 14:e0008876. 2020-12-03 20:11:01.
The yellow fever mosquito and the Southern house mosquito are important vectors of infectious diseases. Given their widespread presence across tropical and subtropical regions of the world and the increased risk of spread due to global warming there is a growing need for population control. Gene drives aim to spread a genetic element within target genes required for mosquito reproduction to disrupt their function and crash a population. Female-specific genes provide interesting candidates for population control since female mosquitoes determine the reproductive capacity of a population as well as being the actual vectors of disease. Here we describe a study on Actin-4 loss in both Aedes aegypti and Culex quinquefasciatus, where we observe female-specific disruption of flight ability and propose it as a candidate for genetic methods of population suppression.
Modelling the Wolbachia incompatible insect technique: strategies for effective mosquito population elimination
15281D. E. Pagendam, B. J. Trewin, N. Snoad, S. A. Ritchie, A. A. Hoffmann, K. M. Staunton, C. Paton and N. Beebe, BMC Biology, 18:13. 2020-12-02 16:29:23.
We introduce a simple Markov population process model for studying mosquito populations subjected to a Wolbachia-IIT programme which exhibit an unstable equilibrium threshold. The model is used to study, in silico, scenarios that are likely to yield a successful elimination result. Our results suggest that elimination is best achieved by releasing males at rates that adapt to the ever-decreasing wild population, thus reducing the risk of releasing Wolbachia-infected females while reducing costs.
Combined Effects of Mating Disruption, Insecticides, and the Sterile Insect Technique on Cydia pomonella in New Zealand
15958R. M. Horner, P. L. Lo, D. J. Rogers, J. T. S. Walker and D. M. Suckling, Insects, 11:23. 2020-11-27 18:11:55.
We aimed to supplement these tactics with the sterile insect technique (SIT) to further suppress the codling moth on orchards. SIT involves mass rearing and sterilizing codling moth and then releasing them onto orchards where they mate with wild insects resulting in no offspring. We released sterile insects onto seven orchards using unmanned aerial vehicles and ground releases. Six years of the program saw significant drops (90-99%) in wild moth populations. The SIT is an excellent tactic for reducing moth populations in export apple orchards.
ARRIGE 2020 Meeting | The promise of CRISPR and gene drive systems to end malaria in Africa
15145E. Gomez-Diaz, ARRIGE org, 2020-11-16 17:08:32.
Presentation by Elena Gómez Díaz (IPBLN-CSIC, Granada, Spain) at the ARRIGE 2020 meeting on "The promise of CRISPR and gene drive systems to end malaria in Africa". Discussion is included at the end of the Ruud de Maagd presentation.https://youtu.be/te3MJ8EZoes
Gene drives, species, and compassion for individuals in conservation biology
15072Y. Rohwer, Ethics, Policy and Environment, 2020-11-10 18:20:29.
In this paper I argue that these compassionate conservationists have a moral obligation to support the investigation and development of genetic modification technologies because of their potential to minimize suffering and eliminate killing in conservation. Furthermore, I will end the paper by suggesting that these genetic technologies can help avoid actions that could be damaging to one's moral character.
When Extinction is Warranted: Invasive Species, Suppression-Drives, and the Worst-Case Scenario
15050A. C. Thresher, Ethics, Policy and Environment, 2020-11-09 19:31:52.
The focus of this paper is on one such risk ? the danger of a suppression-drive escaping containment and wiping out the target species globally. Here, I argue that in most cases this risk is significant enough to warrant holding off on the technology. In some cases, however, we can bypass the precautionary principle by using a dominance approach that hinges on what I term the ?Worst-Case Clause?. This clause, in turn, provides us with a litmus test that can be fruitfully used to determine what species are viable targets for suppression-drives in the wild. Using this metric in concert with other considerations, I suggest that only three species are currently possible viable targets ? the European rabbit, ship rat, and Caribbean Tree Frog.
Gene Drives: A Controversial Tool to Fight Malaria
15008H. Albert, LABIOTECH.eu, 2020-11-09 15:41:52.
The possibility of creating gene drives was introduced into the scientific community in 2003 by Austin Burt, a professor at Imperial College London. Burt was studying ‘selfish genes’ that can copy themselves into a specific target DNA sequence. He suggested that these genes, called homing endonucleases, could be used to make the majority of an organism’s offspring inherit a specific gene, instead of only half of it. This technology has a lot of potential. For example, it could be used to decimate populations of malaria-carrying mosquitoes by making the majority of their offspring male. However, there are concerns about the permanent nature of these genetic modifications and whether it could cause irreparable damage to the ecosystem it is used in.
Expert advises farmers to adopt gene drive-based pest control technology
15029S. Thompson, naija247news, 2020-11-09 15:36:25.
Dr Rose Gidado, County Coordinator, Open Forum on Agricultural Biotechnology(OFAB), has advised farmers to adopt the gene drive-based pest control technology. Gidado, also Deputy Director, National Biotechnology Development Agency (NABDA), said the adoption would significantly help to restore Nigeria’s food crop industry. According to her, Nigerian agricultural system is dominated by the application of synthetic pesticides which have resulted in environmental pollution. Gidado said that it had contributed greatly to climate change, with lethal consequences like increased pest attack, decreased crop yield and extreme heat stress in plants. The scientist said the application of gene drive in Nigeria’s agricultural system, would help greatly in the control of deadly insect pests which cause damages to crops and reduction in food production.
Fighting Mosquito With GMO Mosquito: The Battle Brewing in the Florida Keys
15005S. MacLaughlin, NBC 6 South Florida, 2020-11-06 15:32:04.
Scientists are a few months into an experiment to stop the invasive Aedes aegypti mosquito. Their weapon of choice? A genetically modified mosquito. But some environment advocates question the strategy. This year, the Florida Keys had an outbreak of Dengue fever, which was the first time that had happened in 10 years. It gives new urgency to the controversial effort to get rid of the Aedes aegypti, which has become harder to fight.
Florida will release 750 million genetically modified mosquitoes
14998S. McGlaun, Slash Gear, 2020-11-05 15:14:43.
Local officials in Florida have announced that they have approved 750 million genetically modified mosquitoes to be released into the environment to reduce local populations of the bloodsucking creatures. The goal of releasing genetically modified mosquitoes is to help reduce the number of mosquitoes carrying diseases like dengue or the Zika virus. Approval to release the bugs came after environmental groups warned of unintended consequences.
Is Gene Editing the Answer to Eradicating Malaria in Africa?
14885Staff, ASH Clinical News, 2020-11-01 16:00:02.
Researchers are looking at a new technique to eradicate malaria: Engineering mosquitoes with a “gene drive” – a gene that when inserted into mosquitoes (or other organisms) will be passed on to nearly 100% of the offspring in the next generation, rather than just half the offspring – that rapidly spreads a mutation that removes the insects’ ability to spread the malaria-causing parasite.
Mosquito transgenics and courtship songs
14824H. Hurd, BugBitten BMC, 2020-10-23 17:38:45.
As a female flies into the swarm she is detected by the sound of her wing beat and males identify females by a phonotactic response to the specific sound frequency produced by her wing beat. A male and female will then attune to each other by altering the frequency of their wingbeats in a form of reciprocal tuning that is highly specific.
GeneConvene Global Collaborative Webinar Series | Gene Drive Technical Webinars
14347David O'Brochta and Hector Quemada, GeneConvene Global Collaborative, 2020-10-12 02:54:40.
A series of technical webinars on engineered gene drive technology research and development given by leading researchers in the field.
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.
You should be excited that scientists are releasing 750 million genetically modified mosquitoes this year
14568L. Westreich, Massive Science, 2020-09-27 19:27:28.
GM mosquitoes are successful in reducing mosquito populations, and reducing disease spread
The Con Job at Mosquito Control Board
14571E. Russo and B. Wray, keysnews.com, 2020-09-26 19:32:07.
Shouldn’t there be a consensus among scholars, scientists, experts and the public that this new technology is safe?
Resistance to natural and synthetic gene drive systems
14468T. A. R. Price, N. Windbichler, R. L. Unckless, A. Sutter, J.-N. Runge, P. A. Ross, A. Pomiankowski, N. L. Nuckolls, C. Montchamp-Moreau, N. Mideo, O. Y. Martin, A. Manser, M. Legros, A. M. Larracuente, L. Holman, J. Godwin, N. Gemmell, C. Courret, A. Buc, Journal of Evolutionary Biology, 2020-09-24 17:20:31.
This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in genera
Risks of releasing gene drives mosquitoes – a possible future scenario
15143Testbiotech, 2020-09-17 17:01:45.
Genetically engineering the genome of an organism with gene drive means that it will be replicated in every following generation. This allows the altered gene to spread rapidly throughout natural populations, which may be decimated or even eradicated. The video contains both factual and fictional content (the latter marked as „possible future scenario“). The fictional content shows the possible future consequences of using gene drive technology - and is intended to stimulate broad public debate. Civil society needs to engage intensively with issues around new developments in the field of biotechnology and genetic engineering.
GMOs make war on mosquitoes
14323Staff, Kenosha News, 2020-09-05 15:13:38.
Given that recent record, we were a bit surprised to read that there was a ruckus over genetically modified mosquitoes going on in the Florida Keys.
Why Genetically Modified Mosquitoes Won’t Come to Texas Anytime Soon
14317C. Adams, RA News, 2020-09-04 15:03:04.
Talks about releasing genetically modified mosquitoes in Houston began in 2018 between Harris County and Oxitec, a United Kingdom-based company that produces sustainable technologies or transgenic methodologies to stem the impact of disease-spreading insects. Talk also began about a similar action in Monroe County, Fla.
An accident waiting to happen: Tech company to release 750 MILLION GMO mosquitoes in Florida to fight dengue fever
14232Z. Sky, NEWSTARGET, 2020-08-30 20:31:13.
Oxitec plans to release 750 million OX5034s into the Florida Keys, something that sounds like the beginning of a doomed science-fiction movie. But the most shocking thing here is the fact that Oxitec received the EPA’s approval in May.
Genetically-modified mosquito plan offers hope for Keys, world
14256P. Goodman, keynews.com, 2020-08-29 14:25:12.
The Florida Keys Mosquito Control District Board of Commissioners voted 4-to-1 to approve a trial using Oxitec’s second-generation genetically modified mosquitoes. I
The good mosquito versus the bad
14240D. Datta, Business Standard, 2020-08-29 14:01:00.
Starting 2021, around 750 million genetically modified (GM) Aedes Aegypti mosquitoes will be released in batches into the Florida Keys.
Florida Will Release 750 Genetically Modified Mosquitoes to Stop Disease Spread
14177A. Fahmy, verywell health, 2020-08-28 14:36:32.
The hope is to prevent the spread of Dengue fever, a painful virus acquired only by mosquito bite which made a reappearance in the Florida Keys in 2009.
Evading evolution of resistance to gene drives
14174R. Gomulkiewicz, M. L. Thies and J. J. Bull, bioRxiv, 2020-08-27 14:29:17.
Here we develop mathematical and computational models to identify conditions under which suppression drives will evade resistance, even if resistance is present initially.
Deep dive: Florida’s GM mosquito experiment aims to rewrite rules of vector-borne diseases
14084S. Kannan, India Today, 2020-08-26 14:33:36.
A pathbreaking bioengineering experiment on mosquito populations that could have massive implications for tropical malaria-affected countries like India has got underway in Florida, US.
Fighting mosquito-borne diseases… with mosquitoes
14156N. Gubert and A. Baubeau, Phys Org, 2020-08-26 13:13:41.
For decades, researchers have scratched their heads over how to combat deadly mosquito-borne diseases such as dengue fever.
Bug board OKs release of genetically modified mosquitoes
14151T. O'Hara, keynews.com, 2020-08-26 13:08:07.
After nearly 10 years of debate, the Florida Keys Mosquito Control District board has approved an agreement with biotech company Oxitec to conduct a test release of genetically modified mosquitoes in Monroe County as part of a mosquito limiting or eradication plan.
Genetically modified mosquitoes to be released in the Florida Keys to combat dengue, zika, and yellow fever.
14148Yucatan Times, Yucatan Times, 2020-08-26 13:04:27.
The Florida Keys will be the scene of the first test in the United States with genetically modified Aedes aegypti mosquitoes, an alternative to insecticides and larvicides to end the transmission of diseases such as dengue, zika and yellow fever that has always been surrounded by controversy.
Transgenic moths released to end one of the worst pests on the planet
14099B. Mandalia, Pledge Times, 2020-08-25 14:49:50.
Today the results of the first open field experiment with another of the creations of this biotechnology company are published. It is a variant of the moth Plutella xylostella which is one of the worst agricultural pests in the world.
750 million genetically modified mosquitoes soon released in the wild!
14093explica, explica, 2020-08-25 14:42:52.
Rather frightening mosquitoes will be released on an archipelago in Florida. The goal? Reduce the population of their more dangerous congeners who can transmit certain diseases.
US to Use Genetically Modified Mosquitoes to Fight Dengue Fever
14090H. Badr, Asharq Al-Awsat, 2020-08-25 14:39:32.
After a decade of discussions, officials in Florida have voted to allow the first test in the United States of free-flying, genetically modified mosquitoes that kill any female offspring, as a way to fight the pests and the diseases they spread.
Florida Keys to Use Genetically Modified Mosquitoes to Fight Disease
14087B. Lynn, Voice of America, 2020-08-25 14:33:57.
Officials in the Florida Keys plan to release genetically modified mosquitoes next year in an effort to fight insect-borne diseases.
Florida Approves Controversial Plan to Release 750 Million Genetically Modified Mosquitoes
14096D. Rakshit, Swaddle, 2020-08-24 14:46:17.
Authorities in Florida have approved a pilot project that will release 750 million genetically modified mosquitoes locally, in a bid to reduce the populations of mosquitoes that cause that cause dengue, Zika, chikungunya, and yellow fever
Mutant bugs released to fight disease
14081The Day, The Day, 2020-08-24 14:20:37.
Authorities have approved the scheme in Florida but environmental groups are furious, calling it a “Jurassic Park experiment” that will unleash a “mutant bug” into the ecosystem.
More than 750 million GMO mosquitoes to be released over Florida Keys – what could go wrong?
14145E. Huff, Natural News, 2020-08-24 12:59:20.
The Florida Keys Mosquito Control District (FKMCD) has given Oxitec, a corporation we have reported on in the past, permission to unleash some 750 million GMO mosquitos in Monroe County, Florida, over the next two years.
Florida to release genetically modified mosquitoes to prevent diseases like Zika
14009The West News, The West News, 2020-08-23 17:50:16.
Local authorities on Tuesday gave final approval to release 750 million genetically modified mosquitoes in the Florida Keys over a two-year period, starting in 2021.
Genetically modified mosquitoes have been OK’d for a first U.S. test flight
14003S. Milius, ScienceNews, 2020-08-22 17:44:31.
After a decade of fits and starts, officials in the Florida Keys have voted to allow the first test in the United States of free-flying, genetically modified mosquitoes as a way to fight the pests and the diseases they spread.
Florida Will Release Genetically Modified Mosquitoes to Fight Disease in the Keys
14000S. Harrell, Spectrum News, 2020-08-21 17:40:14.
Following lengthy federal and state procedures, the Florida Keys Mosquito Control District this week approved a plan to release more than 750 million genetically modified mosquitoes in the Keys region to combat an invasive, disease-carrying species of the insect.
Florida is releasing 750 million genetically modified mosquitoes into the world. Here’s why
13992H. Schriber, Deseret News, 2020-08-21 17:35:50.
Florida officials plan to release 750 million genetically modified mosquitoes into the Florida Keys over the next two years as a way to prevent diseases like the Zika virus. The project will begin in 2021. The Environment Protection Agency approved the idea in May. The project will test if one of these mosquitoes can work better than spraying insecticides to stop these insects from spreading potentially fatal viruses, according to CNN.
Genetically Modified Mosquitoes To Be Released In Florida Keys
13989A. Snow, The Daily Wire, 2020-08-21 17:33:00.
CNN reported that the genetically modified bugs, called OX5034, have been “altered to produce female offspring that die in the larval stage, well before hatching and growing large enough to bite and spread disease.” Since it’s the female of the species that bite, they are the ones that carry diseases. Males, the outlet reported, eat nectar.
Release 750 Million Genetically Modified Mosquitoes Into the Wild, They Said
13986C. Delbert, Popular Mechanics, 2020-08-21 17:31:14.
Corporate scientists have received final approval from the Environmental Protection Agency (EPA) to release hundreds of millions of genetically altered mosquitoes into the Florida Keys. The goal? To begin reining in the mosquito population, which is only expected to increase as climate change continues to warm and flood the low-lying, tropical Keys. But some environmental groups object strongly to the move.
Florida releasing genetically modified mosquitoes to prevent diseases like Zika
13984N. Lanese, LiveScience, 2020-08-21 17:29:18.
Hundreds of millions of genetically modified mosquitoes will soon be released in the Florida Keys island chain to wipe out local populations of disease-carrying mosquitoes, according to news reports.
750 Million GM Mosquitoes Will Be Released in the Florida Keys
13982L. Winter, The Scientist, 2020-08-21 17:27:30.
With the aim of reducing rates of the mosquito-borne illnesses yellow fever and dengue, a pilot program will release 750 million genetically modified mosquitoes into the Florida Keys in 2021, thanks to approval by the barrier islands’ Mosquito Control District Board of Commissioners at a meeting on Tuesday (August 18)
Hundreds Of Millions Of Genetically Modified Mosquitoes Approved For Release In US
13996J. Vibes, Anonymous News, 2020-08-20 17:37:24.
A Biotech company called Oxitec has received permission from the government to release hundreds of millions of genetically modified male mosquitoes in the Florida Keys.
Why Hundreds of Millions of Genetically Engineered Mosquitoes Will Soon Be Released in Florida
13979K. Gander, Newsweek, 2020-08-20 17:22:07.
Hundreds of millions of genetically engineered mosquitoes will soon be released in Florida, in a first for the U.S. On Tuesday, the Florida Keys Mosquito Control District (FKMCD) approved plans to release the insects, who do not bite, as part of a pilot project launching next yea
Florida to release genetically modified mosquitoes, detractors blast ‘Jurassic Park’ experiment
13969D. Aaro, Fox News, 2020-08-20 15:49:28.
Local authorities on Tuesday gave final approval to release 750 million genetically modified mosquitoes in the Florida Keys over a two-year period, starting in 2021, with the hope of preventing diseases such as the Zika virus but has faced blowback and comparisons to a Steven Spielberg thriller.
750 million genetically modified mosquitoes to be released across Florida Keys
13966A. Zahid, Sky News, 2020-08-20 15:47:05.
Authorities have approved plans for genetically modified mosquitoes to be released across the Florida Keys from next year. British-based firm Oxitec has designed the project to test whether the altered mosquitoes are a viable alternative to pesticides to control and prevent the spread of diseases, including Zika and dengue.
750 million GM mosquitos set for release in Florida Keys.
13961Editorial Staff, E&T, 2020-08-20 15:43:13.
Local authorities have approved proposals to release hundreds of millions of genetically modified (GM) modified mosquitos in Florida, in an effort to control populations of diseases spread by the organism.
Florida Plans to Fix Its Mosquito Problem With 750 Million More Mosquitoes
13959D. Noor, Gizmodo, 2020-08-20 15:40:34.
Hundreds of millions of mosquitos will soon be released in Florida. On purpose. The mosquitoes are being released as a form of pest control, but they could wreak havoc on local ecosystems.
Florida mosquitoes: 750 million genetically modified insects to be released
13955BBC, BBC, 2020-08-20 15:37:01.
Local officials in Florida have approved the release of 750 million mosquitoes that have been genetically modified to reduce local populations. The aim is to reduce the number of mosquitoes that carry diseases like dengue or the Zika virus.
Florida OKs release of genetically modified mosquitoes in Keys to slow insect disease spread
13952S. Mann, Just the News, 2020-08-20 15:34:23.
Florida officials are authorizing a biotech company to release hundreds of millions of genetically-modified male mosquitoes into the Florida Keys to reduce future mosquito populations that spread diseases including yellow fever and malaria.
Florida Keys to release modified mosqutioes to fight illness
13949C. Anderson, Associated Press, 2020-08-20 15:30:15.
Sometime next year, genetically modified mosquitoes will be released in the Florida Keys in an effort to combat persistent insect-borne diseases such as Dengue fever and the Zika virus. The plan approved this week by the Florida Keys Mosquito Control District calls for a pilot project in 2021 involving the striped-legged Aedes aegypti mosquito, which is not native to Florida.
Florida to Release Millions of Genetically Modified Mosquitoes Against Local Residents’ Wishes
13946N. Rice, People, 2020-08-20 15:27:38.
A plan to release over 750 million genetically modified mosquitoes in the Florida Keys has received final approval. According to CNN, on Tuesday, local authorities approved a plan to release the genetically modified mosquitoes in the Sunshine State's string of islands, with the hope of preventing a string of diseases that the insects can carry.
Plan to Release 750M GMO Mosquitoes Gets Go Ahead
13944R. Quinn, newser, 2020-08-20 15:23:41.
The plan to release the genetically modified Aedes aegypti mosquitoes received final approval from local authorities Tuesday, causing an outcry from groups opposed to what they call a "Jurassic Park experiment," CNN reports.
‘A Jurassic Park Experiment’: Watchdog Groups Denounce Decision to Release Genetically Modified Mosquitoes in Florida
13975L. Newcomb, Common Dreams, 2020-08-19 15:54:09.
Food safety and environmental groups Wednesday condemned a decision by officials in Florida to approve the release of 750 million genetically modified mosquitoes, a pilot project aimed at reducing the spread of mosquito-borne diseases.
Florida Keys to release 750M genetically modified mosquitoes
13972D. Haynes, UPI, 2020-08-19 15:51:58.
Local authorities in the Florida Keys gave their approval Wednesday to a plan to release genetically modified mosquitoes to prevent the spread of dengue fever and other diseases. The Monroe County Mosquito Control District signed off on the project, which would release about 750 million mosquitoes engineered to produce dead offspring.
To combat disease-spreading mosquitoes in the Keys, leaders vote to unleash lab bugs
13964D. Goodhue, Miami Herald, 2020-08-19 15:44:52.
Florida Keys officials have voted to allow the experimental release of millions of genetically modified mosquitoes into a yet-to-be-decided area of the island chain.
Cytoplasmic incompatibility: an autocidal mechanism for mosquito population control
13893V. Dev, BugBitten BMC, 2020-08-18 13:23:13.
Cytoplasmic incompatibility resulting in non-reciprocal fertility is a naturally occurring phenomenon, but remains unexplored to greater extent for the control of insect vector populations. This mechanism deserves priority for mosquito control and reducing disease transmission, being non-insecticidal and easier to operate with minimal investments.
Modelling the suppression of a malaria vector using a CRISPR-Cas9 gene drive to reduce female fertility
13724A. R. North, A. Burt and H. C. J. Godfray, BMC Biology, 18:98. 2020-08-11 12:23:41.
Gene drives based on CRISPR-Cas9 technology are increasingly being considered as tools for reducing the capacity of mosquito populations to transmit malaria, and one of the most promising options is driving endonuclease genes that reduce the fertility of female mosquitoes. Here, we use simulation modelling to understand the factors affecting the spread of this type of gene drive over a one million-square kilometre area of West Africa containing substantial environmental and social heterogeneity.
Maintenance management and eradication of established aquatic invaders
13936D. Simberloff, Hydrobiologia, 22. 2020-08-06 13:34:15.
The rapid development of technologies based on genetics has engendered excitement about possibly eradicating or controlling terrestrial invaders, and such technologies may also prove useful for certain aquatic invaders. Methods of particular interest, alone or in various combinations, are gene-silencing, RNA-guided gene drives, and the use of transgenes.
Modeling the suppression dynamics of Aedes mosquitoes with mating inhomogeneity
13847M. Huang and L. Hu, Journal of Biological Dynamics, 14:656-678. 2020-08-04 13:51:41.
In this work, we introduce a delay differential equation model with mating inhomogeneity to discuss mosquito population suppression based on Wolbachia. Our analyses show that the wild mosquitoes could be eliminated if either the adult mortality rate exceeds the threshold δ∗A or the release amount exceeds the threshold r∗ uniformly. Our simulations suggest that the releasing should be started at least 5 weeks before the peak dengue season, taking into account both the release amount and the suppression speed.
A One-Sided Competition Mathematical Model for the Sterile Insect Technique
14287A. Ben Dhahbi, Y. Chargui, S. M. Boulaaras and S. Ben Khalifa, Complexity, 2020:12. 2020-07-30 13:59:01.
We study a simple mathematical model describing the dynamics of a wild-type pest insects population experiencing competition from sterile insects (one-sided competition).
Nix alone is sufficient to convert female Aedes aegypti into fertile males and myo-sex is needed for male flight
13780A. Aryan, M. A. E. Anderson, J. K. Biedler, Y. M. Qi, J. M. Overcash, A. N. Naumenko, M. V. Sharakhova, C. H. Mao, Z. N. Adelman and Z. J. Tu, Proceedings of the National Academy of Sciences of the United States of America, 117:17702-17709. 2020-07-28 13:17:04.
Here, we report the generation of multiple transgenic lines that express Nix under the control of its own promoter. Genetic and molecular analyses of these lines provided insights unattainable from previous transient experiments. We show that the Nix transgene alone, in the absence of the M-locus, was sufficient to convert females into males with all male-specific sexually dimorphic features and male-like gene expression.
Tackling Dengue fever by turning female mosquitoes into males
13482T. Sandle, DIGTAL JOURNAL, 2020-07-22 21:00:41.
T. Sandle (2020). DIGTAL JOURNAL Genetic engineering appears to be the key for delivering mosquito control, according to new research. Scientists have successfully converted female mosquitoes into non-biting males.
Researchers convert female mosquitoes to nonbiting males with implications for mosquito control
13194Virginia Tech, ScienceDaily, 2020-07-14 18:12:22.
Researchers convert female mosquitoes to nonbiting males with implications for mosquito control Virginia Tech researchers have proven that a single gene can convert female Aedes aegypti mosquitoes into fertile male mosquitoes and identified a gene needed for male mosquito flight
Role of gene drives in malaria elimination strategy: modeling impact and cost-effectiveness in the Democratic Republic of the Congo
12729N. Metchanun, C. Borgemeister, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin, medRxiv, 2020-06-29 13:15:39.
The tremendous burden of malaria has led to renewed efforts on malaria elimination and the development of novel tools for application where existing tools fall short. Gene drive mosquitoes, where transgenes and their associated phenotypes are efficiently propagated to future generations, are under development to suppress vector populations or render vectors incapable of malaria transmission. However, the role of gene drives in an integrated elimination strategy is underexplored. Using a spatially explicit agent-based model of malaria transmission in the Democratic Republic of the Congo, we describe the impact of integrating a population suppression driving-Y gene drive into malaria elimination strategies. We find that as long as the driving-Y construct is extremely effective, releases of gene drive mosquitoes can eliminate malaria, and we identify a cost ceiling for gene drive to be cost-effective relative to existing tools. Vector control via gene drive is worth considering as a supplemental intervention when the construct parameters and costs are suitable.
Analysis of a Strong Suppressor of Segregation Distorter inDrosophila melanogaster
14264R. G. Temin, Genetics, 215:1085-1105. 2020-06-19 14:59:33.
These studies highlight the polygenic nature of distortion and its dependence on a constellation of positive and negative modifiers, provide insight into the stability of Mendelian transmission in natural populations even when a drive system arises, and pave the way for molecular characterization ofSu(SD)whose identity should reveal new information about the mechanism of distortion.
ENSSER | Gene Drive Webinar Series
12568European Network of Scientists for Social and Environmental Responsibility, 2020-06-16 20:50:52.
This series of five Webinars by some of the authors of the interdisciplinary Gene Drive Report (2019) and were organised by four organisations of independent scientists: the European Network of Scientists for Social and Environmental Responsibility (ENSSER), Critical Scientists Switzerland (CSS), Vereinigung Deutscher Wissenschaftler (VDW), Sciences Citoyennes (SC). The series was aimed at a lay audience and were intended to address these questions. Does it really work? Is it being applied? What problems do gene drives address? What side effects can they have? Who has an interest in this? Should we do it? Are gene drives regulated by law? Are they a wise solution to these problems? Who decides?
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.
The malaria mosquito is eliminated in the lab by creating a population of all males
11611NewsDesk, Instant, 2020-05-11 16:08:42.
A team led by Imperial College London disseminates genetic modification that distorts the sex ratio through the Anopheles gambiae mosquito population that is locked up using ‘gene drive’ technology.
Gene editing and the war against malaria
11226E. Bier and E. Sobber, American Scientist, 102:162. 2020-04-16 15:34:38.
Malaria is a devastating disease transmitted from person to person by mosquitoes. It kills more than 400,000 people per year, more than half of those deaths being children 5 years old or younger. CRISPR (clustered regularly interspaced short palindromic repeats) is a new gene-editing technology that acts like a pair of molecular scissors: It is used to “cut and paste” DNA sequences to alter gene function. In “Gene Editing and the War Against Malaria” (pages 162–169), Ethan Bier and Elliott Sober describe how biologists can now alter genes in a malaria-transmitting mosquito population by engineering a CRISPR gene drive, which mimics a natural evolutionary process. With this tool, a new gene can be inserted into the genome so that the alteration is rapidly passed down to successive sexually reproducing generations. Two gene-drive strategies have been found feasible: The first drives a local malaria-transmitting population to extinction; the second renders mosquitoes unable to transmit malaria, which breaks the malaria transmission cycle.
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.
Antiviral effectors and gene drive strategies for mosquito population suppression or replacement to mitigate arbovirus transmission by Aedes aegypti
6634A. E. Williams, A. W. E. Franz, W. R. Reid and K. E. Olson, Insects, 11:1-18. 2020-01-12 20:05:33.
The mosquito vector Aedes aegypti transmits arthropod-borne viruses (arboviruses) of medical importance, including Zika, dengue, and yellow fever viruses. Controlling mosquito populations remains the method of choice to prevent disease transmission. Novel mosquito control strategies based on genetically manipulating mosquitoes are being developed as additional tools to combat arbovirus transmission. Genetic control of mosquitoes includes two basic strategies: population suppression and population replacement. The former aims to eliminate mosquito populations while the latter aims to replace wild populations with engineered, pathogen-resistant mosquitoes. In this review, we outline suppression strategies being applied in the field, as well as current antiviral effector genes that have been characterized and expressed in transgenic Ae. aegypti for population replacement. We discuss cutting-edge gene drive technologies that can be used to enhance the inheritance of effector genes, while highlighting the challenges and opportunities associated with gene drives. Finally, we present currently available models that can estimate mosquito release numbers and time to transgene fixation for several gene drive systems. Based on the recent advances in genetic engineering, we anticipate that antiviral transgenic Ae. aegypti exhibiting gene drive will soon emerge; however, close monitoring in simulated field conditions will be required to demonstrate the efficacy and utility of such transgenic mosquitoes.
Design and analysis of CRISPR-based underdominance toxin-antidote gene drives
5626Champer, J., S. E. Champer, I. Kim, A. G. Clark and P. W. Messer, bioRxiv, 861435:861435. 2019-12-17 16:38:34.
CRISPR gene drive systems offer a mechanism for transmitting a desirable transgene throughout a population for purposes ranging from vector-borne disease control to invasive species suppression. In this simulation study, we model and assess the performance of several CRISPR-based underdominance gene drive constructs employing toxin-antidote principles. These drives disrupt the wild-type version of an essential gene using a CRISPR nuclease (the toxin) while simultaneously carrying a recoded version of the gene (the antidote). Drives of this nature allow for releases that could be potentially confined to a desired geographic location. This is because such drives have a nonzero invasion threshold frequency, referring to the critical frequency required for the drive to spread through the population. We model drives which target essential genes that are either haplosufficient or haplolethal, using nuclease promoters with expression restricted to the germline, promoters that additionally result in cleavage activity in the early embryo from maternal deposition, and promoters that have ubiquitous somatic expression. We also study several possible drive architectures, considering both “same-site” and “distant-site” systems, as well as several reciprocally targeting drives. Together, these drive variants provide a wide range of invasion threshold frequencies and options for both population modification and suppression. Our results suggest that CRISPR toxin-antidote underdominance drive systems could allow for the design of highly flexible and potentially confinable gene drive strategies.
Identification and characterisation of a Masculinizer homolog in the diamondback moth Plutella xylostella
5607Harvey-Samuel, T., V. C. Norman, R. Carter, E. Lovett and L. Alphey, Insect Molecular Biology, 2019:2019. 2019-12-17 16:09:12.
Recently, a novel sex-determination system was identified in the silkworm (Bombyx mori) in which a piRNA encoded on the female-specific W chromosome silences a Z-linked gene (Masculinizer) which would otherwise initiate male sex-determination and dosage compensation. Masculinizer provides various opportunities for developing improved genetic pest management tools. A pest lepidopteran in which a genetic pest management system has been developed, but which would benefit greatly from such improved designs, is the diamondback moth, Plutella xylostella. However, Masculinizer has not yet been identified in this species. Here, focusing on the previously described ?masculinizing? domain of B. mori Masculinizer, we identify P. xylostella Masculinizer (PxyMasc). We show that PxyMasc is Z-linked, regulates sex-specific alternative splicing of doublesex and is necessary for male survival. Similar results in B. mori suggest this survival effect is possibly through failure to initiate male dosage compensation. The highly conserved function and location of this gene between these two distantly related lepidopterans suggests a deep role for Masculinizer in the sex-determination systems of the Lepidoptera.
Scientists release sterile mosquitoes in Burkina to fight malaria
17024T. Ndiaga, Reuters, 2019-09-18 13:18:20.
Scientists in Burkina Faso have deployed a new weapon in the fight against malaria, and waded into a thorny bioethics debate, by letting loose thousands of genetically sterilized mosquitoes.Their experiment is the first outside the lab to release genetically altered mosquitoes in the hope of reducing their ability to spread the often deadly disease. It works using a technique called a gene drive, which edits and then propagates a gene in a population - in this case to prevent males from producing offspring. Investments in anti-malarial drugs, mosquito nets and insecticides have slowed malaria over the past two decades in Africa, which accounts for more than 90% of global cases. But malaria still killed more than 400,000 people across the continent in 2017, and the World Health Organization says progress against the disease is stalling, leading researchers to push for fresh approaches.
Viral gene drive in herpesviruses
5917Walter, M. and E. Verdin, bioRxiv, 2019:717017. 2019-07-30 16:38:14.
Herpesviruses are ubiquitous pathogens in need of novel therapeutic solutions. Current engineered gene drive strategies rely on sexual reproduction, and are thought to be restricted to sexual organisms. Here, we report on the design of a novel gene drive system that allows the spread of an engineered trait in populations of DNA viruses and, in particular, herpesviruses. We describe the successful transmission of a gene drive sequence between distinct strains of human cytomegalovirus (human herpesvirus 5) and show that gene drive viruses can efficiently target and replace wildtype populations in cell culture experiments. Our results indicate that viral gene drives can be used to suppress a viral infection and may represent a novel therapeutic strategy against herpesviruses.
Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs
3895Buchman, AG, S.; Li, M.; Antoshechkin, I.; Li, H. H.; Wang, H. W.; Chen, C. H.; Klein, M. J.; Duchemin, J. B.; Paradkar, P. N.; Akbari, O. S., Proceedings of the National Academy of Sciences of the United States of America, 116:3656-3661. 2019-01-13 00:00:00.
Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive-based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered synthetic small RNAs targeting ZIKV is expressed and fully processed in Aedes aegypti, ensuring the formation of mature synthetic small RNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.
The ethical implications of population suppression and the irreversibility of gene drives
14167J. Kim, International Journal of Life Sciences Research, 2018-04-01 14:11:25.
This paper aims to examine the current situation by presenting important ethical arguments that include Chardin’s principle of irreversibility and Weiss’ beliefs on intergenerational equity, ideals upheld by the United Nations
Strong hybrid male incompatibilities impede the spread of a selfish chromosome between populations of a fly
4024Verspoor Rudi, LSJ, M. L.; Mannion Natasha, L. M.; Hurst Gregory, D. D.; Price Tom, A. R., Evolution Letters, 2:169-179. 2018-01-02 00:00:00.
Meiotically driving sex chromosomes manipulate gametogenesis to increase their transmission at a cost to the rest of the genome. The intragenomic conflicts they produce have major impacts on the ecology and evolution of their host species. However, their ecological dynamics remain poorly understood. Simple population genetic models predict meiotic drivers will rapidly reach fixation in populations and spread across landscapes. In contrast, natural populations commonly show spatial variation in the frequency of drivers, with drive present in clines or mosaics across species ranges. For example, Drosophila subobscura harbors a sex ratio distorting drive chromosome (SRs) at 15?25% frequency in North Africa, present at less than 2% frequency in adjacent southern Spain, and absent in other European populations. Here, we investigate the forces preventing the spread of the driver northward. We show that SRs has remained at a constant frequency in North Africa, and failed to spread in Spain. We find strong evidence that spread is impeded by genetic incompatibility between SRs and Spanish autosomal backgrounds. When we cross SRs from North Africa onto Spanish genetic backgrounds we observe strong incompatibilities specific to hybrids bearing SRs. The incompatibilities increase in severity in F2 male hybrids, leading to almost complete infertility. We find no evidence supporting an alternative hypothesis, that there is resistance to drive in Spanish populations. We conclude that the source of the stepped frequency variation is genetic incompatibility between the SRs chromosome and the genetic backgrounds of the adjacent population, preventing SRs spreading northward. The low frequency of SRs in South Spain is consistent with recurrent gene flow across the Strait of Gibraltar combined with selection against the SRs element through genetic incompatibility. This demonstrates that incompatibilities between drive chromosomes and naïve populations can prevent the spread of drive between populations, at a continental scale.
Ecological and evolutionary applications for environmental sex reversal of fish
11518A. McNair, P. M. Lokman, G. P. Closs and S. Nakagawa, Quarterly Review of Biology, 90:23-44. 2015-03-01 15:38:29.
Environmental sex reversal (ESR), which results in a mismatch between genotypic and phenotypic sex, is well documented in numerous fish species and may be induced by chemical exposure. Historically, research involving piscine ESR has been carried out with a view to improving profitability in aquaculture or to elucidate the processes governing sex determination and sexual differentiation. However, recent studies in evolution and ecology suggest research on ESR now has much wider applications and ramifications. We begin with an overview of ESR in fish and a brief review of the traditional applications thereof We then discuss ESR and its potential demographic consequences in wild populations. Theory even suggests sex-reversed fish may be purposefully released to manipulate population dynamics. We suggest new research directions that may prove fruitful in understanding how ESR at the individual level translates to population-level processes. In the latter portion of the review we focus on evolutionary applications of ESR Sex-reversal studies from the aquaculture literature provide insight in to the evolvability of determinants of sexual phenotype. Additionally, induced sex reversal can provide information about the evolution of sex chromosomes and sex-linked traits. Recently, naturally occurring ESR has been implicated as a mechanism contributing to the evolution of sex chromosomes.
Sperm traits of masculinized fish relative to wild-type males: a systematic review and meta-analyses
11512A. M. Senior, S. L. Johnson and S. Nakagawa, Fish and Fisheries, 17:143-164. 2014-09-11 15:29:18.
Environmental sex reversal (ESR), whereby environmental effects (e.g. exogenous chemicals) override genetic sex determination, is a commonly used technique in aquaculture and physiology research. We performed a systematic review and meta-analyses of the literature that compares the sperm characteristics of masculinized genotypic females to wild-type males. We detected no mean differences between the ejaculate volume, sperm motility, duration or linearity of each type of male. We found some large mean differences in sperm concentration (d=2.541, CI=-0.004 to 5.086), reproductive success (d=-1.400, CI=-2.943 to 0.142), semen osmolality (d=1.850, CI=0.622 to 3.077) and sperm velocity (d=-0.933, CI=-1.426 to -0.441); in the case of the latter two traits, the mean effect was statistically significant. However, any significance did not stand up to a more conservative analysis. Additionally, heterogeneity was high and we found that where large differences between the sperm of sex-reversed and wild-type males are reported, these effects are attributable to sperm sampling methodology. Overall, we found little evidence for large systematic differences between the sperm produced by masculinized and wild-type male fish. Thus, masculinized genotypic females may enjoy reproductive success comparable to genotypic males. This conclusion leads to two potential implications: (i) sex-reversed fish may influence the dynamics of wild populations and (ii) aquaculture practices may use ESR to produce males with sperm quality similar to that of genotypic males. Most studies appear to have been performed in aquaculture species (i.e. Salmonidae); thus future experiments in non-model organisms may provide important insights in to the uniformity of the effects described.
Sterility introduced by release of genetically altered males to a domestic population of Aedes aegypti at the Kenya coast
25875P. T. McDonald, W. Hausermann and N. Lorimer, Am J Trop Med Hyg, 26:553-61. 1977-05-06 07:09:31.
The release of males heterozygous for one or two sex-linked translocations was effective in introducing a high level of sterility into a domestic population of Aedes aegypti at a Rabai village. The effect of the releases continued for several weeks after the release period. Male mosquitoes, Aedes aegypti, were released at the Kenya coast to test the effectiveness of laboratory engineered mosquitoes in introducing a genetic mechanism and the ability of the mechanism to establish itself under field conditions. A triplicate of Rabai villages was selected for the experiment. In the 1st village nottreatment was made. In the 2nd village the domestic water containers were cleaned twice a week to remove larvae and pupae. Translocation males were released in the 3rd village. A mixture of 2 types of males was introduced: the single heteroxygote male selected from 78 translocations induced by irradiation in the African strains, and the double heterozygote male. Genetic analysis of the content of release samples determined quality control of released males. Fertility was also determined with females of a strain collected at Chibarani before releases began. Hatchability of eggs in all villages was counted to assay sterility in all villages. Before the releases population fluctuations in the 3 villages were monitored for 20 weeks. The release mixture had a fertility of 37% and the single heterozygote of 50%. A daily survival rate of .63 was shown for the dusted release males. There was close agreement between the monitoring for sterility for both the egg collections and the oviposition of the LB catch females. The sterility introduced into the Chibarani population was extensive.
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