Scholarly Literature
This is an aggregation of scholarly literature from peer-reviewed journals, bioRxiv , medRxiv and arXiv preprint servers focused on natural and engineered selfish genetic elements and genetic biocontrol. New citations are added as they appear. This content is intended for anyone interested in the scholarly literature on gene drive and genetic biocontrol.
“Target species complex” concept: Strengthening environmental risk assessment of engineered gene drives
35531J.B. Connolly, Y. Devos, D.C.M. Glandorf, and J. Romeis, Proc. Natl. Acad. Sci., 2026-03-30 19:11:30.
The recent opinion piece of Christophe Boëte critiqued the concept of the target species complex (TSC) in environmental risk assessment (ERA) of engineered gene drives (EGDs) (1). While constructive debate is essential, the piece misrepresents the purpose of TSC and conflates unrelated mechanisms, creating misconceptions that merit clarification. Malaria-transmitting mosquitoes often belong to species complexes, comprising vector and nonvector species, where hybridization can be detected in laboratory settings and occasionally in the field (2–4). Low-threshold EGDs are self-sustaining and nonlocalizing (5). Should such EGD be released in a species complex where target genomic sequences are conserved, in the event of interspecific mating in the field vertical gene drive transfer (VGDT) to nonvector species could occur, potentially harming biodiversity protection goals. Conversely, VGDT to vector species could advance health objectives (6).
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.
Editorial Overview – Insect Genomics (2026): enhancing public health, food security, and biodiversity through genetic biocontrol.
35506Yoosook Lee, Omar S. Akbari, Current Opinion in Insect Science, 2026-03-13 09:43:24.
Genetic biocontrol is a form of biological control in which genetic variants or genetically modified forms of the target species act to reduce or eliminate the target species. In entomology, target species include agricultural pests and vector species that transmit pathogens to human, animal, or plant systems. Examples include the Anopheles mosquito gene drive system to reduce or replace malaria vectors in Africa, the use of Wolbachia symbiont induced cytoplasmic incompatibility in Culex mosquitoes to project Hawaiian native birds from avian malaria related deaths, and the use of CRISPR to generate sterile males at a scale useful for suppressing pests of fruit crops. The widespread availability of robust transgenic technologies combined with new RNA-guided DNA endonuclease-based genome manipulation technologies and platforms and advances in synthetic biology are fueling the development of genetic biocontrol technologies and systems for combating arthropods that contribute to food insecurity, pathogen- and parasite-transmission, and invasive arthropods that threaten biodiversity. Heretofore a niche area of genetic biocontrol now commands great interest and an ever-growing number of applications.
Regulatory Provisions for Post-Release Monitoring of Genetically Modified Organisms in Africa
35497Julia Njagi, John Muriuki, Paul Mbugua, et al., Frontiers in Bioengineering and Biotechnology, 2026-03-10 09:22:44.
Genetically modified (GM) crops with improved traits such as resistance to biotic and abiotic stresses and enhanced nutritional profiles have been commercially cultivated for over three decades. Despite extensive safety data and long-term cultivation experience, concerns continue to be raised about the potential risks and benefits of genetically modified organisms (GMOs). This is particularly true for the African region, where only eight out of fifty-four countries have so far commercialized GMOs. Upon release into the environment, GM crops may interact with ecosystems in complex ways, possibly leading to unanticipated ecological effects. Consequently, post-release monitoring of GMOs is essential to identify early signs of adverse impacts, enabling timely responses such as adjustments in risk management strategies, mitigation measures, or re-evaluation of previous regulatory decisions. A supportive policy and regulatory environment are critical for facilitating the safe development, testing, and commercialization of GMOs. This study conducted a desktop review of post-release monitoring frameworks for GMOs in selected African countries, as well as interviews with key informants in countries that have commercialized at least one GMO product. The findings reveal that most sampled countries lack clearly defined environmental protection goals and specific provisions regarding the scope and duration of post-release monitoring of GMOs. Where the duration of monitoring is prescribed, it is a blanket cover for all GMOs regardless of their life cycles. Moreover, the responsibility for monitoring is often delegated entirely to the applicant, and where local institutions are involved, there is no clear coordination mechanism for data sharing. These findings underscore the need for case-by-case monitoring approaches, guided by clearly articulated national protection goals and clear roles and coordination among stakeholders to ensure the safe and responsible deployment of GMOs.
Modelling Aedes albopictus management, incorporating immigration and bi-directional Wolbachia interactions
35520Ryan, M., Mendiolar, M., Pagendam, D. et al., J Pest Sci, 99. 2026-03-10 09:16:51.
Aedes albopictus mosquitoes are competent vectors for the spread of at least 24 different arboviruses, including dengue, Ross River, and Japanese encephalitis viruses. However, they remain less studied than their more urban cousins, Aedes aegypti. We model an incompatible insect technique (IIT) strategy for mosquito control, with bi-directional incompatibility between two strains of Wolbachia (wAlbA/wAlbB ARwP) and age-based cytoplasmic incompatibility decay in a well-mixed population. We include mosquito immigration to explore potential reversibility, an important consideration in bi-directional IIT control programs. We also explore the establishment probability after female contamination of an artificially-infected Wolbachia mosquito strain, consider the suppression dynamics and probability of mosquito management success for different release strategies, and determine a corresponding cost proxy for release (numbers of mosquitoes released). We found an establishment probability threshold of 40% in the absence of mating preferences, though this threshold needs validation in future field and laboratory experiments. We found differences in suppression success between release cessation and 6 months later for different immigration rates. There are similar short-term costs with differences in medium- and longer-term costs between release strategies. Our model suggests bi-directional IIT control programs are reversible with low amounts of wild-type immigration. This work demonstrates opportunities to optimise the suppression of these medically important mosquitoes.
Mark–release–recapture study of irradiated male Aedes albopictus under stressful field conditions
35492Qingdeng Feng, Ming Li, Jeremy Bouyer, et al., Pest Management Science, 2026-03-09 10:33:54.
The sterile insect technique (SIT) suppresses mosquito populations by releasing sterile males. Its success mainly depends on the performance of sterile males. Mark–Release–Recapture (MRR) experiments are used to evaluate male performance in the field, yet most previous experiments were conducted under mild conditions (e.g. 25–28 °C) in which mosquitoes could easily adapt. Male mosquito performance under stressful field conditions remains poorly understood. This study evaluated the field performance of irradiated Aedes albopictus males under high-temperature conditions (>30 °C in average) in southern China, Foshan City, located in a sub-tropical area. Two MRR experiments were conducted in a 5-ha village during July–August of 2023 and 2024. Lifespan and dispersal of postreleased males were examined using BG-Sentinel mosquito traps, human landing catches, and ovitraps. A total of 54 546 and 58 440 sterile males were released in 2023 and 2024, respectively, with recapture rates of 8.53% and 5.64%. The mean dispersal distances ranged from 58.88–77.19 m (2023) to 81.82–90.86 m (2024). Daily survival probabilities were 0.15–0.28 in 2023 and 0.45–0.62 in 2024, corresponding to average expected lifespans of 0.53–0.78 days and 1.26–2.13 days, respectively. Estimated wild male densities ranged from 302–986 males ha−1 in 2023 to 416–3785 males ha−1 in 2024. Stressful field conditions severely reduced sterile male survival and dispersal, highlighting the need to optimize release protocols in challenging climates. These findings provide critical baseline data for advancing Ae. albopictus SIT programmes in southern China.
Advances in male sex separation for the support of mosquito control programs
35526Duman-Scheel M, Frontiers in Insect Science, 6. 2026-03-09 09:05:10.
Several mosquito control technologies, including the sterile insect technique (SIT), the incompatible insect technique (IIT), and a variety of genetic technologies are emerging as promising solutions for combatting insecticide resistance and the spread of vector-borne diseases. These approaches involve mass releases of male mosquitoes in an effort to suppress mosquito populations in an eco-friendly manner. At small scale, male mosquito selection can be achieved through the use of mechanical separation techniques, but such methods are not sufficient for scaled implementation of emerging mosquito population control technologies. This review discusses mechanical, genetic, and automated mosquito sex sorting techniques that have emerged to address the need for scaled male mosquito production, as well as the potential contributions of RNA interference (RNAi) to facilitate this process. One RNAi method utilizes the oral delivery of yeast expressing interfering RNA targeting genes required for female larval survival. The yeast, which can be incorporated into normal insect larval diets, enables male sex selection during larval rearing in mosquitoes and could easily be extended to other insects. RNAi-mediated sex-sorting technologies, in combination with mechanical, genetic, and automated sorting technologies, could facilitate the scaled production of adult males in support of global insect population suppression efforts.
Discovery of a Genetic Toxin-Antidote System in Vertebrates
35490Duilio Mazzoni Zerbinato A Silva, Morgan Skinner, Takaya Totsuka, et al., bioRxiv, 2026-03-06 10:25:21.
Toxin-antidote (TA) systems are selfish genetic elements that bias their own inheritance by coupling a toxin that kills daughter cells or offspring with an antidote that specifically rescues those with the TA. TAs are a widespread phenomenon, observed in bacteria, fungi, plants, and invertebrate animals, but have not yet been described in vertebrates. Here we report the first known vertebrate TA system that sabotages mammalian embryogenesis. The HSR locus on mouse chromosome 1 is a selfish genetic element that biases its transmission through the female germline. When HSR heterozygous females are crossed with wild-type males, wild-type embryos show high mortality, leading to preferential survival of embryos with HSR. The mechanism underlying embryo killing was unknown. We find that HSR kills wild-type post implantation embryos by depositing a toxin (SP100) that induces significant DNA damage. Embryos with HSR also inherit the toxin but survive by expressing an antidote (SP110) that blocks the effects of the toxin. Our findings reveal a previously unrecognized genetic cheating strategy in vertebrates and demonstrate its impact on mammalian reproduction.
Optimal spatial release strategies for confined gene drives and Wolbachia
35488Ziye Wang, Jackson Champer, bioRxiv, 2026-03-06 10:19:13.
Gene drives are genetic elements that can rapidly spread through populations, offering potential solutions for controlling disease vectors and pests. In some scenarios, it is necessary to utilize drives that can be confined to only target populations. The success of these threshold-dependent gene drives, which require a minimum local frequency to establish, depends critically on the spatial strategy used for introduction. Here, we use a reaction-diffusion model to systematically identify optimal release patterns that maximize the per-capita efficiency for four distinct gene drive designs as well as use of Wolbachia bacteria, which spread similarly to frequency-dependent gene drives. We find that the most efficient release strategy is highly dynamic, transitioning from a broad "everywhere" release for short timeframes to a "multiple-ring" pattern for intermediate times, and finally to a focused "center" release for longer timeframes. These timeframes depend on the specific type of drive, with more powerful variants transitioning more quickly to center releases. Our results demonstrate that these optimized, variable release strategies can be substantially more effective than simple uniform releases. This study provides a quantitative framework for designing effective gene drive implementations, highlighting that a carefully planned spatial strategy is essential for maximizing impact, making optimal use of available resources.
Wolbachia wMel and wAlbB strains differentially impact the vector competence of Aedes aegypti with a Brazilian genetic background for DENV-1 virus
35484Martins, C.B., David, M.R., Couto-Lima, D. et al., Parasites Vectors, 2026-03-05 08:32:23.
Aedes aegypti mosquitoes infected with the endosymbiotic bacterium Wolbachia pipientis have been released as a sustainable strategy to mitigate arbovirus transmission. Among the strains successfully deployed, wMel and wAlbB have shown promising blocking effects against dengue virus (DENV). However, the strength of viral inhibition depends on Wolbachia density within mosquito tissues, the genetic backgrounds of both host and virus, and the viral dose. In this study, we aimed to investigate the vector competence for DENV-1 of Ae. aegypti with Brazilian genetic background infected with wMel or wAlbB. A total of 493 wild and wMel- and wAlbB-infected mosquitoes were orally challenged with low (5 × 104 FFU/mL) and high (5 × 105) titers of DENV-1. Relative Wolbachia density was measured by quantitative polymerase chain reaction (qPCR), and viral infection in mosquito bodies and saliva was assessed by qPCR with reverse transcription (RT-qPCR). Transmission potential was tested through saliva microinjection into susceptible mosquitoes. The infection prevalence and viral loads in mosquito bodies were analyzed at 7, 14, and 21 days post infection (dpi).Both Ae. aegypti groups infected with wMel and wAlbB had reduced (albeit distinct) DENV-1 infection and transmission relative to wild type mosquitoes. wMel-infected mosquitoes exhibited less abundant bacteria in their bodies but a greater degree of DENV-1 inhibition compared with those carrying wAlbB, indicating that DENV-1 blocking is strain specific rather than Wolbachia density-driven. Moreover, we observed that Wolbachia had a protective effect on mosquitoes by decreasing the DENV-1 loads in their bodies, but with a constant presence of virus. Viral transmission rates in the saliva were similar among wild and wMel- and wAlbB-infected mosquitoes at 7 and 14 dpi but lower in wMel and wAlbB mosquitoes at 21 dpi. The similar DENV-1 loads in mosquito bodies over time (7, 14, and 21 dpi) infected with either the wMel or wAlbB strain, regardless of the viral titer of the infectious blood meal, suggest that Wolbachia may have a maximum pathogen-blocking capacity beyond which additional virus suppression cannot be achieved. The viral suppression only after 21 dpi in the saliva raises concerns and warrants further investigation, as females may transmit before Wolbachia blockage becomes effective. While wAlbB may exhibit comparable DENV-1 blocking to wMel, its enhanced thermal tolerance makes it epidemiologically relevant in tropical regions. Continuous monitoring of Wolbachia dynamics and DENV genomic variation in the field remains essential to evaluate long-term effectiveness and detect potential adaptive viral responses.
Comparison of single-cell sequencing technologies for allele-specific expression analysis in rabbit spermatids
35482Elena Smertina, Madi Rutherford, Brendan Hosking, et al., Genomics, 2026-03-05 08:26:37.
Gene drives are transmission distorters that can transmit specific alleles to >90% of the progeny, e.g., the naturally occurring t-haplotype in mice. For invasive pest species, there is interest in co-opting naturally occurring gene drives. It is unknown whether similar natural gene drives exist in the European rabbit, one of the most detrimental pest species in Australia. Here, we analysed the allele-specific expression (ASE) in rabbit spermatids to identify candidate genes for future investigation in genetic biocontrol applications. We utilised short-read and long-read technologies and performed a comparative analysis. Illumina sequencing was deemed unsuitable, whereas both long-read sequencing platforms demonstrated a similar performance. The SPINK2 gene that plays an important role in fertility, consistently showed ASE towards one of the alleles in all samples. Furthermore, two kinases were found to display a bimodal allele expression. Future work is warranted to assess suitability of these genes for genetic biocontrol applications.
Present and Future of Mosquito-Borne Disease Control in Europe with a Specific Focus on the Mediterranean
35535Cholvi, M., Moretti, R., Osório, H. C., et al., Insects, 17. 2026-02-27 19:18:24.
Mosquito-borne diseases are an emerging public health challenge in Europe, driven by the spread of invasive mosquito species capable of sustaining outbreaks of tropical arboviral diseases. Rising temperatures, shifting precipitation patterns, human-driven habitat changes, and prolonged transmission seasons have increased the risk of dengue, chikungunya, and West Nile virus outbreaks, among other vector-borne diseases. Effective control requires a multifaceted approach, combining traditional and novel methods with advanced surveillance technologies and community involvement. However, growing insecticide resistance and concerns about insecticide use highlight the need for more prudent management of current tools and the development of innovative alternatives. Genetic control strategies, including the Sterile Insect Technique (SIT), Wolbachia-based approaches, and genetically modified (GM) mosquitoes, offer promising solutions but still face scientific, regulatory, and societal challenges. This review explores the current landscape of mosquito-borne disease control in Mediterranean Europe, emphasizing key challenges and emerging solutions. An integrated approach that strengthens surveillance, promotes sustainable control methods, and incorporates novel biotechnological tools supported by smart technologies will be essential to reduce the future burden of mosquito-borne diseases in the region.
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.
Locally Acquired Dengue in Townsville, Australia, 2024–2025: An Outbreak Report in a Non-Endemic Region with wMel Wolbachia-Infected Aedes aegypti
35533Thompson, K., Lyons, S., Malone, K., Fryk, J., Pyke, A., & Murton, K., Tropical Medicine and Infectious Disease, 11. 2026-02-26 19:11:49.
During the 2024/2025 wet season, Townsville had its first sustained autochthonous outbreak of dengue disease caused by dengue virus type 2 (DENV-2), the second locally transmitted outbreak of dengue since 2014 following the introduction of wMel strain Wolbachia-infected mosquitoes, a control strategy for dengue virus (DENV) and other Aedes-transmitted arboviruses. In comparison to two recorded locally acquired cases of dengue in 2020, the 2024/2025 outbreak resulted in sixteen cases in two inner-city suburbs of Townsville during the wet season associated with higher-than-average rainfall. This second dengue outbreak since 2014 highlights that Townsville and other north Queensland communities where Wolbachia mosquito programs have been deployed remain vulnerable to DENV incursions and local disease outbreaks despite the apparent high coverage of Wolbachia-infected mosquitoes. Whilst these control strategies have likely contributed to a reduction in the number and frequency of autochthonous DENV outbreaks in north Queensland, ongoing maintenance and monitoring of Wolbachia-infected mosquito coverage is necessary, together with timely review and improvement in dengue awareness and prevention health promotion activities in the community.
Ecological analysis of mosquito larval communities in Burkina Faso to inform environmental monitoring of genetic control programs
35470Toé, I., Kientega, M., Lingani, A.J. et al., Scientific Reports, 16. 2026-02-24 14:26:04.
In Burkina Faso, the development of the gene drive technology targeting Anopheles coluzzii raises important ecological questions about potential non-target effects. Understanding interactions in mosquitoes’ natural environments is crucial for developing effective post-release environmental safety monitoring. This study assesses the ecological exposure and potential risks to non-target organisms associated with An. coluzzii suppression. Using co-occurrence, niche overlap metrics, and characterisation of physicochemical parameters, we evaluated interspecific relationships among mosquitoes and macroinvertebrate taxa from larval habitats in Burkina Faso. Combined index revealed distinct ecological relationships, ranging from competitive or facilitative coexistence to spatial segregation driven by predation or behavioural avoidance. Based on these interactions, an exposure score was developed to quantify the potential susceptibility of non-target organisms to ecological changes following the removal of An. coluzzii. The results showed variable exposure among taxa, with An. gambiae s.s. having the highest score, followed by An. arabiensis and Culex spp. Predatory taxa such as Corixidae showed niche overlap but limited spatial co-occurrence, suggesting effective predation. The detection of hybrid forms (An. coluzzii x An. gambiae s.s.) further highlights the potential for gene flow. This study introduces a quantitative framework that combines ecological indices and exposure scores to predict potential risks to non-target organisms.
Stochastic dynamics at the back of a gene drive eradication wave
35468Léna Kläy, Léo Girardin, Florence Débarre, Vincent Calvez, Theoretical Population Biology, 168:44-64. 2026-02-24 14:22:40.
Gene drive alleles bias their own inheritance to offspring. They can fix in a wild-type population in spite of a fitness cost, and even lead to the eradication of the target population if the fitness cost is high. However, this outcome may be prevented or delayed if areas previously cleared by the drive are recolonised by wild-type individuals. Here, we investigate the conditions under which these stochastic wild-type recolonisation events are likely and when they are unlikely to occur in one spatial dimension. More precisely, we examine the conditions ensuring that the last individual carrying a wild-type allele is surrounded by a large enough number of drive homozygous individuals, resulting in a very low chance of wild-type recolonisation. To do so, we make a deterministic approximation of the distribution of drive alleles within the wave, and we split the distribution of wild-type alleles into a deterministic part and a stochastic part. Our analytical and numerical results suggest that the probability of wild-type recolonisation events increases with lower fitness of drive individuals and with smaller local carrying capacity. Numerical simulations show that these results extend to two spatial dimensions. The role of the migration rate however, is less clear but has a lower impact. We further demonstrate that, in the event of wild-type recolonisation, the probability of subsequent drive reinvasion decreases with smaller values of the intrinsic growth rate of the population. Overall, our study paves the way for further analysis of wild-type recolonisation at the back of eradication travelling waves.
A distorter–restorer system drives quantitative reproductive isolation in rice
35461Zhang, Y., Yang, Y., Shi, C. et al., Nature Plants, 2026-02-24 10:08:29.
Hybrid sterility and segregation distortion are the major forms of postzygotic reproductive isolation in rice, yet the molecular basis of their quantitative variation remains unclear. Here we identify S44, a natural distorter–restorer system in Oryza longistaminata/Asian cultivated rice hybrids, comprising four tightly linked elements—Reproductive Isolation Distorter (RID), Reproductive Isolation Restorer (RIR), Reproductive Isolation Activator (RIA) and Reproductive Isolation Suppressor (RIS)—which collectively regulate hybrid male sterility and segregation distortion. The distorter RID triggers the elimination of O. sativa cultivar RD23 pollen, whereas the restorer RIR selectively safeguards O. longistaminata gametes, thereby preferentially transmitting its allele into the progeny. RIS and RIA fine-tune segregation distortion. We further demonstrate that the allelic conflicts at the S44 locus drive quantitative reproductive isolation between O. longistaminata and other rice lineages, and CRISPR-engineered RID knockout can universally overcome S44-mediated reproductive barriers in the AA genome, enabling revolutionary cross-species breeding. This distorter–restorer system provides a unique genetic module for deciphering speciation mechanisms and advancing crop breeding strategies.
Spatial confinement of gene drives: Assessing risk of failure using global sensitivity analysis
35459Cole D. Butler, Alun L. Lloyd, bioRxiv, 2026-02-19 09:59:30.
Gene drives allow pest populations to be genetically modified to reduce their harm on agriculture and human health. The genetic modification, or payload, spreads within a target population at rates exceeding normal Mendelian inheritance. While gene drives have demonstrated immense potential in laboratory populations, they present unique challenges. Foremost among these challenges is spatial confinement, or ensuring that the payload remains confined to target populations. However, there is an inherent tension between gene drive spread and spatial confinement: increasing the spreading efficiency of a gene drive increases the risk of escape, while engineering confinement mechanisms increases the risk of gene drive extinction. In this work, we explore spatial outcomes in gene drives designed for spatial confinement and the dependence of these outcomes on target organism dispersal and payload fitness cost. We use a stochastic spatial model to compute the probability of failure for each gene drive, and use techniques from global sensitivity analysis to quantify the contribution of dispersal and fitness cost to variance in gene drive performance. Our findings reveal how spatial outcomes are affected by key parameters, and how this sensitivity varies tremendously between different gene drives. These spatial properties can be used to classify gene drive behavior and are useful to determine suitability for a particular application.
Upper bound on the mutational burden imposed by a CRISPR-Cas9 gene-drive element
35463Michael S Overton, Sean E Guy, Xingsen Chen, et al., G3 Genes|Genomes|Genetics, 2026-02-18 10:08:37.
Homing-based CRISPR-Cas9 gene drives (CCGDs) are powerful tools for genetic control of wild populations, with applications from disease eradication to species conservation. However, Cas9 alone and in a complex with guide RNA can cause double-stranded DNA breaks at off-target sites, which could increase the mutational load and lead to unintended loss-of-heterozygosity (LOH) events. These undesired effects raise potential concerns about the long-term evolutionary safety of CCGDs, but the magnitude of these effects is unknown. To measure how the presence of a CCGD or a Cas9 alone in the genome affects the rates of LOH events and de novo mutations, we carried out a mutation accumulation experiment in yeast Saccharomyces cerevisiae. We found no detectable effects on the genome-wide rates of mutations or LOH events. Our power calculations suggest that CCGD or Cas9 affect these rates by less than 30%, which is much less than natural variation for these traits in yeast. A more detailed examination shows that CCGD or Cas9 may alter the lengths and genomic distributions of LOH events, but the statistical support for these effects is weak. Thus, our results demonstrate that CCGDs impose at most a weak additional mutational burden in the yeast model. Although mutagenic effects of gene drives need to be further evaluated in other systems, our results add credence to the proposition that the evolutionary risks posed by well-designed gene drives may be acceptable.
Evaluation of local larval diets for mass rearing of Aedes aegypti to support sterile insect technique programs in Burkina Faso Get
35466Bouraïma Vincent Séré, Simon P Sawadogo, Prisca S L Paré, et al., Journal of Medical Entomology, 63. 2026-02-16 14:16:30.
Aedes aegypti Linnaeus 1762 is the primary vector of several viruses that cause arboviral diseases. Control strategies, such as SIT, require large-scale mosquito (Diptera: Culicidae) production, which depends critically on larval nutrition. However, the high cost and limited availability of conventional feed components hinder SIT implementation, particularly in resource-limited settings. Faced with this situation, it is imperative to find locally produced food sources. Here, we assessed six locally derived diets for their suitability in mass rearing Aedes aegypti. The diets include: (B) African Clarias gariepinus Burchell 1822 (Siluriformes: Clariidae) dried without additives; (C) Cirina butyrospermi Vuillet 1911 (Lepidoptera: Saturniidae) dried without additives; (D) Glycine max (L.) Merr., 1917 without additives; (E) a 1:1 mixture of Clarias gariepinus and Cirina butyrospermi; (F) a 1:1 mixture of Clarias gariepinus and Glycine max; and a mixture of 50% Clarias gariepinus, (G) 25% Glycine max and 25% Cirina butyrospermi. (A) Commercial fish food formulation (TetraMin® Baby) served as the control. Diets C and D were associated with significantly delayed while diets C, D, and E yielded fewer adults than the control. In contrast, diets B and G provided the most favorable balance of development time, adult emergence, and survival, comparable to the control group. Diets D and F produced the lowest fecundity and hatch rates, whereas diet G generated large, fertile adults. Collectively, these findings indicate that diets B and G are suitable for mass rearing, with diet G emerging as a cost-effective alternative for SIT programs targeting Aedes aegypti in Burkina Faso.
Advances in CRISPR gene drives for mosquito population control
35449Robyn Raban, Anthony A James, Omar S Akbari, Current Opinion in Microbiology, 90. 2026-02-12 19:25:19.
CRISPR-based gene drive (GD) systems bias allele inheritance during meiosis, enabling transgenes to spread at rates exceeding Mendel’s law of segregation. This capability underlies their potential as powerful tools for controlling mosquito-borne diseases. GDs can be engineered either to suppress mosquito populations or to modify them by introducing traits that block pathogen transmission. Recent advances have focused on improving evolutionary stability, with modeling studies providing insights into expected population dynamics. With a focus on the most current population modification GDs, we discuss advances in GD architectures — including integral and allelic drives, combined modification–suppression systems, and both homing and non-homing toxin–antidote designs — that expand the range of possible strategies and address limitations of early homing drives. Numerous antipathogen effectors with strong pathogen-blocking activity can now be coupled to these systems, with current efforts assessing their durability against genetically diverse pathogens. Key challenges remain, including resistance evolution, ecological impacts, and long-term stability. Nonetheless, GDs offer a promising approach for reducing disease transmission, especially in regions where conventional interventions are difficult to sustain.
Mathematical modelling of Wolbachia replacement in Aedes aegypti for dengue control: a scoping review
35445Katie Tiley, Laith Yakob, Kathleen O'Reilly, Oliver Brady, Proc Biol Sci, 293. 2026-02-12 17:52:03.
Wolbachia replacement in dengue virus vectors is a promising tool for controlling transmission, and models can explore its potential in novel and complex scenarios. We analyse how research questions in Wolbachia replacement modelling have developed over time and in response to empirical findings. A scoping review was conducted of Wolbachia replacement models. For each study, we extracted research questions, key findings and modelling methodology and thematically categorized research questions. From 726 search results, 115 studies met inclusion criteria. Four themes were identified: identifying key Wolbachia characteristics (n = 61, 53.0%), investigating effects of environmental heterogeneity (n = 21, 18.3%), estimating epidemiological impact (n = 25, 21.7%) and exploring Wolbachia replacement in combination with other arboviral control measures (n = 8, 7.0%). Models identify cytoplasmic incompatibility (CI) and maternal transmission (MT) as key for fixation success. However, less than 20% (n = 6) of studies parameterize CI and MT using empirical sources. Although models agree outbreaks may occur with fixation, few explore epidemiological outcomes of heterogeneous Wolbachia fixation or combined vector control. These findings highlight the need for empirical parameterization and incorporating environmental complexity for models to remain insightful for decision-making. Policymakers would benefit from future models exploring heterogeneous coverage and combined control strategies, given evidence of context-specific outcomes and diverse control tools.
Dengue Suppression by Male Wolbachia-Infected Mosquitoes
35443Jue Tao Lim, Ph.D., Chee-Seng Chong, Ph.D., Chia-Chen Chang, Ph.D., et al., New England Journal of Medicine, 2026-02-12 17:46:04.
Wild-type female Aedes aegypti mosquitoes that mate with male A. aegypti mosquitoes that have been infected with the wAlbB strain of Wolbachia pipientis bacteria produce nonviable offspring owing to cytoplasmic incompatibility. Repeated releases of wolbachia-infected males can potentially suppress wild-type mosquito populations and reduce the risk of dengue virus infection. We conducted a trial involving the release of male A. aegypti mosquitoes infected with the wAlbB strain of wolbachia bacteria for the control of dengue in Singapore, a tropical city-state. In this cluster-randomized trial with test-negative controls, we divided 15 geographic population clusters into two groups: 8 clusters received deployments of male wolbachia-infected mosquitoes (intervention clusters) and 7 clusters received no deployments (control clusters). The primary end point was the diagnosis of symptomatic dengue virus infection of any severity caused by any serotype of the virus, as measured by the odds ratio for the distribution of wolbachia exposure among laboratory-confirmed reported dengue cases as compared with test-negative controls. A total of 393,236 residents lived in the intervention clusters, and 331,192 lived in the control clusters. Adult wild-type A. aegypti populations were suppressed across the intervention clusters. The baseline average abundance of the mosquitoes (number of adult female mosquitoes trapped divided by number of traps) was 0.18 and 0.19 in the intervention and control clusters, respectively; from 3 months after the initiation of the intervention until the end of the 24-month trial period, the average abundance was 0.041 and 0.277, respectively. In the intention-to-treat analysis at 6 months or more, the percentage of residents in the intervention clusters who were dengue-positive was lower than that in the control clusters (354 of 5722 tests [6%] vs. 1519 of 7080 tests [21%]). The protective efficacy of the intervention, calculated as (1−odds ratio)×100, ranged from 71 to 72% with 3 to 12 months or more of wolbachia mosquito exposure, as represented by odds ratios of 0.28 to 0.29. Release of sterile wolbachia-infected male A. aegypti mosquitoes reduced vector populations and the risk of dengue infection in Singapore.
Evaluating paratransgenesis using engineered symbiotic bacteria for Plasmodium inhibition in mosquito vectors: A systematic review
35538Cleanclay WD, Kernyuy FB, Kintung IF, et al, PLoS Neglected Tropical Diseases, 2026-02-12 16:54:19.
Malaria is one of the key world health problems, especially in sub-Saharan Africa, where the rising resistance to insecticides and antimalarial drugs is posing a threat to the current control mechanisms. New strategies are urgently needed to break the cycle of the spread of Plasmodium parasites by the Anopheles mosquito. A potential solution is paratransgenesis, which involves the genetic modification of naturally occurring mosquito-associated microbes to produce molecules that prevent the development of parasites in the gut of the mosquito. In this systematic review, we examined experimental studies that investigated paratransgenesis as a malaria control measure. Using the PRISMA guideline, we identified ten eligible studies that had engineered bacterial or fungal symbionts to express antiplasmodial effector proteins. These studies showed that feeding mosquitoes a sugar meal containing engineered microbes resulted in a stable colonization of the mosquito midgut. Several of the molecules tested were highly effective in reducing parasite development, with scorpine consistently showing strong transmission-blocking activity, achieving parasite inhibition rates greater than 90% in different experimental systems. Inhibitory effects were also further augmented by the combination of several effector molecules. Overall, the finding suggests that paratransgenesis has strong potential as an additional malaria control measure. Nevertheless, contests concerning ecological safety, microbial stability, and field implementation will need to be solved before large-scale implementation can be done.
Signatures of sex ratio distortion in humans
35441James Guy Baldwin-Brown, Sergiusz Wesolowski, Raquel Mae Reisinger, et al., bioRxiv, 2026-02-10 18:42:47.
Segregation distortion, the disproportionate inheritance of selfish genetic elements, is an important evolutionary force. While many species carry distorters, it is not clear if humans do. Major limitations for detecting human distortion are the small size of human families and the lack of genetic markers in most subjects. Here, we present evidence of strong distortion in a large human pedigree. We analyzed pedigrees from the Utah Population Database and identified lineages with a high chance of carrying a distorter. In particular, we identified a family that preferentially produced male offspring at a 2:1 ratio. This pattern is consistent with a distorting Y-chromosome, a rarity in species with degenerate Y-chromosomes. The detection of such non-Mendelian inheritance patterns suggests that human genomes may harbor segregation distorters.
The evolution of the sterile insect technique from concept to global application
35432Kostas Bourtzis, Marc F. Schetelig, Walther Enkerlin, Rui Pereira, Comprehensive Molecular Insect Science, 5:180-211. 2026-02-10 12:07:51.
The sterile insect technique (SIT) is a species-specific, environment-friendly and cost-effective method for controlling insect pests and disease vectors. It involves colonization and mass-rearing of the target species, sterilization, typically by ionizing radiation, and systematic release of sterile insects, preferably males, into the target area. Released sterile males induce reproductive failure in wild populations, leading to suppression, containment, prevention of establishment, or local eradication of a target insect pest population. First demonstrated over a century ago, SIT has evolved into a robust and widely adopted tool within area-wide integrated pest management (AW-IPM) programs. It has been successfully applied against several major agricultural and veterinary pests, often achieving high returns on investment. In the context of accelerating climate change and global species invasions, further development and deployment of SIT are essential. Future efforts should focus on enhancing cost-effectiveness, operational scalability, and integration with complementary technologies for sustainable pest and vector management.
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.
Emerging trends in genome editing of wild animals
35453Blix, T., Myhr, A.I., Transgenic Research, 35. 2026-02-06 09:37:20.
Globally, nearly one million species are currently threatened with extinction, highlighting the need for more efficient solutions to biological conservation. Genome editing, which allows for faster and more precise changes in genomes, is a promising technique for boosting populations through facilitated adaptation, management of invasive or pathogenic populations, and potentially even facilitating the revival of extinct species. These approaches belong to a new field of research termed conservation biotechnology, which places a great responsibility on researchers and decision makers to ensure sustainability. In this paper, we have mapped the emerging trends in genome editing of wild animals. Current projects primarily focus on population control and de-extinction, with fewer initiatives aimed at preserving threatened species. We then explore four critical dimensions of conservation biotechnology: the technology itself, new perspectives on conservation practices, research organization, and governance and policy. Despite its potential, key questions remain—particularly whether genome editing can increase genetic diversity without causing unintended non-target impacts. Genome editing also provokes new perspectives on conservation practices where ecosystem-wide impact assessment, case-by-case evaluations, and post-release monitoring needs to be prioritized. Furthermore, conservation biotechnology is heavily funded through private funding showing varying stakeholder interest, which can lead to untraditional and less transparent research processes. Stakeholders, including local and indigenous people, are only to a certain degree involved, which may weaken inclusion of local knowledge and monitoring efforts. Finally, concerning governance and policy, there is an urgent need to develop more adequate regulation of conservation biotechnology, as environmental release of genome-edited animals challenges definitions and guidelines in current nature protection laws and GMO regulations. Based on our analysis, we outline key points for further investigation toward a more sustainable approach to conservation biotechnology.
Generating cisgenic sexing strains in insect pests
35435Davydova, S., Liu, J., Kandul, N.P. et al., Communications Biology, 2026-02-05 18:20:56.
Insect pest population control via sterile insect technique markedly benefits from separation by sex prior to release. To simplify this process, traditional genetics has been deployed to develop genetic sexing strains (GSSs) for several disease vectors and agricultural pests of vast economic significance, although very few are applied in the field due to associated fitness costs and instability. In this study, we generated a method to engineer cisgenic GSS (CGSS) in insects. We use CRISPR/Cas9-mediated homology-directed repair to seamlessly translocate a sex-specific alternatively spliced intron into a dominant phenotypic gene generating a genetically stable strain that enables sex-sorting by eye. To achieve this feat, we use Ceratitis capitata as our model and relied on the sex-specifically spliced intron of its endogenous transformer gene, which we seamlessly inserted a copy into the pupal colouration white pupae gene. This minimal modification resulted in the generation of a homozygous strain we term IMPERIAL that was genetically and phenotypically stable where all female pupae are brown while male pupae are white with overall good fitness. By minimally editing the genome, our novel CGSS approach can be applied to other pests that may aid more efficient and economically suitable pest control.
A conjugal gene drive-like system efficiently suppresses antibiotic resistance in a bacterial population
35426Kaduwal, S., Stuart, E.C., Auradkar, A. et al., npj Antimicrobials and Resistance, 4. 2026-02-05 10:30:00.
Antibiotic resistance (AR) is an escalating public health threat, necessitating innovative strategies to control resistant bacterial populations. One promising approach involves engineering genetic elements that can spread within microbial communities to eliminate AR genes. Previously, we developed Pro-Active Genetics (Pro-AG), a CRISPR-based gene-drive-like system capable of reducing AR colony-forming units (CFU) by approximately five logs. Here, we advance this technology by integrating Pro-AG into a conjugative transfer system, enabling efficient dissemination of an anti-AR gene cassette between two bacterial strains. Additionally, we characterize a complementary homology-based deletion (HBD) process, a CRISPR-driven mechanism that precisely removes target DNA sequences flanked by short direct repeats. Our findings reveal that Pro-AG and HBD are differentially influenced by the bacterial RecA pathway and that HBD components can be delivered via plasmids or phages to selectively delete Pro-AG cassettes. This built-in safeguard prevents uncontrolled spread of a gene cassette and mitigates unanticipated side effects. These refinements enhance the efficiency and flexibility of Pro-AG, expanding its potential applications in microbiome engineering, environmental remediation, and clinical interventions aimed at combating antibiotic resistance. More broadly, this work establishes a proof-of-principle for microbiome engineering strategies that could be leveraged to improve health and restore ecological balance.
Precision pest management: Genome editing tools, specifically CRISPR/Cas9 and future prospects
35424Ankush Saini, Neha Sharma, Nidhi Sharma, et al., Pesticide Biochemistry and Physiology, 218. 2026-02-03 15:42:17.
The growing resistance to synthetic insecticides and Bt toxins, alongside persistent crop losses despite heavy pesticide application, highlights the urgent need for safer, sustainable and efficient pest management strategies. This review presents genome editing as a precise and versatile approach to reduce pest impact by altering fertility, feeding patterns or vulnerability, while protecting beneficial organisms. Among the genome editing tools, CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) is one of the most promising genome editing techniques in insects. It facilitates targeted functional studies, integration with RNAi and dual-expression systems and gene drive applications. Deployment is envisioned in two phases, initial laboratory modification followed by regulated field release, with a strong emphasis on biosafety through terminator genes, marked individuals for gene flow monitoring, optimized dosages, stringent screening and long-term ecological surveillance, along with transparency and adherence to international safety protocols. Significant challenges encompass delivery efficiency, identification of edits, off-target mutations, dose-related efficacy and sterility, unstable transmission and resistance development. Innovations such as base and prime editing minimize unintended mutations by circumventing double-stranded breaks (DSBs), while paratransgenic strategies targeting gut symbionts offer supplementary avenues; plant-mediated insect gene editing emerges as a promising frontier. Overall, carefully regulated trials aligned with policy frameworks and stakeholder involvement are vital to assess effectiveness in natural environments and achieve targeted, dependable and ecologically responsible pest control.
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.
Serratia species as paratransgenic vehicles: potential applications in vector-borne disease control
35422Mahor S, Gupta H. 0., Clinical Microbiology Reviews, 2026-02-02 15:13:09.
Paratransgenesis employs insect-associated bacteria to deliver antipathogen effectors and is an emergent complementary strategy for vector control. This review synthesizes current evidence for Serratia species as paratransgenic vehicles, combining mechanistic insights into effector molecules (e.g., scorpine, MP2, multi-fusion constructs, and the naturally secreted antimalarial lipase AmLip), with comparative evidence on colonization, transmission, and efficacy. Serratia strains (e.g., AS1, Su_YN1) demonstrate rapid dissemination in laboratory populations and potent reductions in Plasmodium development (reported oocyst inhibition in laboratory studies ranging from ~60% to >90% for specific effectors). We critically examine biosafety, genetic stability, and ecological factors and propose a minimum evidence package and translational roadmap comprising multigeneration stability assays, horizontal gene transfer monitoring, non-target impact assessments, and community and regulatory engagement to responsibly advance Serratia-based paratransgenesis toward field evaluation. This comparative framing integrates Serratia-focused detail with the broader paratransgenesis literature to clarify both its promise and remaining knowledge gaps.
Biocontrol practitioners’ perspectives on emerging genetic-based technologies for weed management
35412Rafter, M.A., Kumaran, N., Brookes, D.R. et al., BioControl, 2026-01-31 16:43:25.
Weed biocontrol researchers have been at the forefront of developing management solutions for invasive weeds for over 100 years and have a unique perspective to offer on the emerging field of genetic-based technologies such as gene drive and RNAi. As part of the XVI International Symposium on Biological Control of Weeds in May 2023 we conducted a focus group discussion workshop to explore biocontrol practitioners’ perspectives related to: (1) Genetic-based control technologies, and the factors influencing support (or not) for their application to weed management, especially weed biocontrol, (2) perceived opportunities to apply genetic-based control tools to enhance or complement weed biocontrol, focusing on whether/how genetic tools can be applied to fundamentally change the practice of weed biocontrol, and (3) genetic-based control in weed management and how it can operate within the Access and Benefit Sharing regulatory landscape. We analyse the perspectives of biocontrol scientists from the workshop and discuss the prospects and challenges of integrating novel genetic-based control tools with weed biocontrol.
Mapping Gene Drive Dynamics onto Mendelian Models
35414Zihang Wen, Monica Wan, Gili Greenbaum, Oana Carja, bioRxiv, 2026-01-30 16:46:40.
CRISPR-based gene drives bias their own transmission and can spread even when deleterious, giving rise to evolutionary dynamics that can be substantially more complex than those governed by standard Mendelian inheritance. Identifying conditions under which gene-drive dynamics can be faithfully approximated by Mendelian models would therefore enable the extensive theoretical toolkit of classical population genetics to be applied to gene-drive systems. Here, we develop a general mapping framework that translates gene-drive models into dynamically equivalent Mendelian models, allowing their behavior to be analyzed using classical theory. By deriving both haploid and diploid effective-parameter mappings, we identify Mendelian models that closely reproduce allele-frequency trajectories of gene drives across a wide range of conversion rates, fitness costs, and dominance effects. We delineate the regions of the parameter space where a one-parameter haploid approximation provides an accurate first-order representation, and where incorporating dominance in a diploid mapping substantially improves fidelity and recovers internal equilibria and threshold behavior. Analytic approximations yield efficient mappings across most of the drive parameter space, while a trajectory-based grid search further improves accuracy near nonlinear regime boundaries. To demonstrate the utility of this framework, we apply it to predicting gene swamping in a two-deme migration-selection model and show that the mapped Mendelian system accurately forecasts transitions between fixation and loss under three relevant release scenarios: environmental variation in fitness, engineered fitness asymmetries, and environment-dependent conversion. Together, these results establish a theoretical bridge between non-Mendelian gene drives and classical population genetic models, providing an interpretable and computationally efficient foundation for predicting gene-drive outcomes and guiding the design of gene drive systems and deployment strategies.
The Evolutionary Genomics of Meiotic Drive
35407Daven C Presgraves, R Kelly Dawe, Kelly A Dyer, et al., Molecular Biology and Evolution, 2026-01-23 16:40:29.
Meiotic drivers are selfish genetic elements that gain transmission advantages by distorting equal, Mendelian segregation. For decades, biologists have considered meiotic drivers as interesting, albeit esoteric, case studies. It is now clear, however, that meiotic drive is more common and phylogenetically widespread than previously supposed. Indeed, intensive study of a few well-known cases has begun to reveal the evolutionary genomic consequences of meiotic drive. We argue here that many features of genome evolution, content, and organization that are seemingly inexplicable by organismal adaptation or nearly neutral processes are instead best accounted for by recurrent histories of meiotic drive. We review how meiotic drive can affect the evolution of sequences, gene copy numbers, genes with functions in meiosis and gametogenesis, signatures of “selection”, chromosome rearrangements, and karyotype evolution. We also explore the interactions of meiotic drive elements with other classes of selfish genetic elements, including satellite DNAs, transposable elements, and with the endogenous host genes involved in drive suppression. Finally, we argue that some aspects of drive-mediated genome evolution are now sufficiently well established that we might reverse the direction of discovery— rather than ask how drive affects genome evolution, we can use genome data to discover new putative drive elements.
Bisexual releases are as effective as male-only releases to control Drosophila suzukii with the sterile insect technique
35393Alexandra Labbetoul, Simon Fellous, Pest Management Science, 2026-01-23 10:16:56.
The sterile insect technique (SIT) suppresses insect reproduction by repeatedly releasing sterile insects and allowing them to mate with insects of the same species in the wild. While the classical SIT relies on sterile males mating with wild females, there is a debate regarding the risks and benefits of releasing sterile females along with the sterile males (i.e. bisexual releases). In a replicated cage experiment, we compared the effect of unisexual and bisexual sterile releases of Drosophila suzukii on induced sterility. To ensure field-realism, fertile females - wild-F0 freshly emerged from field-collected sweet-cherries - were placed in cages with artificial vegetation and plastic berries. The proportion of fertile females that produced offspring was not significantly different in unisexual and bisexual treatment (45% and 46%, respectively). Excluding females that had not mated (i.e. no sperm in the spermathecae) from the analysis had no influence. These results suggest the release of sterile females does not always affect the efficacy of the SIT. Even though additional phenomena may arise when scaling up from cages to the field, we conclude that sorting females with genetic constructs or robotic systems is probably dispensable in D. suzukii SIT, at least when deployed in confined farming systems.
D. melanogaster meiotic driver Stellate compromises sperm development by impeding a process of nuclear envelope remodeling
35390Xuefeng Meng, Yukiko M Yamashita,, Genetics, 2026-01-23 09:55:19.
Meiotic drive is a phenomenon that violates Mendel’s Law of Equal Segregation, leading to biased transmission of the meiotic driver to the offspring. D. melanogaster Stellate (Ste) is an X-linked meiotic driver that preferentially harms Y-chromosome-bearing spermatids, thereby favoring the transmission of the X chromosome to the next generation. We have recently shown that Ste protein segregates asymmetrically during meiosis I with a strong bias toward the Y-chromosome-inheriting side, leading to the eventual demise of the Y-chromosome-containing spermatids. However, the cellular mechanisms by which Ste protein interferes with spermatid development remain unknown. Here, we show that Ste-containing spermatids are delayed in the process of nuclear envelope remodeling, an essential process during sperm DNA compaction. We show that components of the nuclear lamina (such as Lamin Dm0, and the LEM domain proteins Otefin and Bocks) are rapidly removed during nuclear envelope remodeling during the early stages of normal spermatid development. However, Ste-containing spermatids retained these nuclear lamina proteins for a prolonged time. Their delayed removal is associated with defective formation of the dense complex, which is composed of a bundle of microtubules and serves as a structural support for sperm nuclear morphogenesis. Defective dense complex formation in Ste-containing spermatids led to defective sperm DNA compaction. Together, the present study reveals an unexpected cellular mechanism by which a meiotic driver, Ste, sabotages sperm development.
Targeted editing of pericentromeric satellite DNA alters sensitivity to meiotic drive
35388Danna G. Eickbush, Jabale Rahmat, Matthew Lindsay, et al., bioRxiv, 2026-01-21 16:51:02.
Eukaryotic genomes are abundant in satellite DNA (satDNA): large blocks of tandemly-repeated sequences that accumulate in heterochromatic genome regions. SatDNAs are dynamic in their genomic location and abundance across species. Some satDNAs overlap essential genome regions such as centromeres and telomeres, but even pericentromeric satDNA can have effects on phenotypes, raising questions about their functional significance. However, it remains unclear whether these effects depend on satDNA sequence, copy number, higher-order structural organization, or genomic context. The highly repetitive nature of satDNA arrays has long hindered detailed genomic and genetic analyses. Recent advances in long-read sequencing now facilitate both the detailed characterization of satDNA structure and the development of more targeted approaches to genetic analysis. Here we present a sequential CRISPR/Cas9-based strategy to make mutations in satDNA arrays and demonstrate its utility using an autosomal pericentromeric satDNA in Drosophila melanogaster called Responder (Rsp). Rsp is the target of a sperm-killing male meiotic driver, Segregation Distorter (SD), where sensitivity to sperm killing positively correlates with Rsp copy number. Using our CRISPR/Cas9 approach, we generated an allelic series of Rsp deletion and expansion variants in two genetic backgrounds and examined their effects on spermatogenesis. Our approach produced precise satDNA variants efficiently, with minimal detectable off-target effects. The resulting mutations affect sensitivity to SD that scale with Rsp copy number. This work establishes a new framework for experimentally dissecting satDNA function and provides insights into the evolutionary and functional roles of satDNA in genome organization.
Drive, suppression and escape from suppression of a selfish chromosome
35382Jackson Ridges, Jackson Bladen, Robert Unckless, Nitin Phadnis, Proc Biol Sci, 21. 2026-01-21 13:39:59.
Meiotic drivers are selfish genetic elements that are predicted to spark rapid intra-genomic arms races with their suppressors. However, the long-term persistence of unsuppressed selfish chromosomes in natural populations violates these theoretical expectations. The Drosophila pseudoobscura Sex-Ratio (SR) chromosome exemplifies this problem, sometimes referred to as the ‘ancient gene drive paradox’. Here, we analyse the evolutionary history of this SR chromosome and show that its genetic architecture and complexity have likely been shaped by a history of drive, suppression and escape from suppression. Our results suggest that the current lack of resistance to the SR chromosome may represent a transient condition awaiting the emergence of new suppressors.
Microhomology-mediated end joining is the predominant form of DNA repair in the mosquito Aedes aegypti with implications for gene editing, gene drive, and transgene removal
35375Joseph S Romanowski, Kevin M Myles, Zach N Adelman, Nucleic Acids Research, 54. 2026-01-20 16:30:25.
Programmable site-specific nucleases have revolutionized the field of genetics, and in the field of mosquito vector control, gene editing by these tools has inspired a new wave of population control approaches that aim to prevent disease transmission. Little is known of how DNA repair is prioritized in mosquitoes, which diverged from the nearest model system (Drosophila) by >200 million years, despite site-specific gene editing now being commonplace. Here, we report a scalable, high-throughput platform for studying DNA double-stranded DNA break (DSB) repair in mosquitoes by delivering CRISPR/Cas9, I-SceI, or other nucleases to Aedes aegypti embryos, capable of measuring single-strand annealing (SSA), non-homologous end joining, and microhomology-mediated end-joining (MMEJ) repair outcomes. We find CRISPR/Cas9 can induce deletions of up to 8.6 kb through SSA repair and is tolerant of resection distances of 3.5 kb. Indel events were insensitive to lig4 knockouts, and across 20 synthetic guide RNAs (sgRNAs) representing 5 locations in 2 transgenic strains were almost exclusively attributed to MMEJ repair, establishing MMEJ as the dominant form of repair in A. aegypti at CRISPR/Cas9 DSBs. This information is critical to our understanding of how DNA repair shapes processes required for genetic control strategies involving gene drive action/resistance as well as transgene stability.
Assessing the population genetic structure and demographic history of Anopheles gambiae and Anopheles arabiensis at island and mainland sites in Uganda: implications for testing novel malaria vector control approaches
35384Mwima, R., Hui, TY.J., Lukyamuzi, E. et al., Malar J, 2026-01-20 13:40:12.
Despite substantial investments in malaria control, the disease remains a major burden in sub-Saharan Africa, particularly Uganda. Novel tools such as gene drive systems are being developed to suppress malaria vector populations, but their deployment requires detailed knowledge of mosquito population genetics. The genetic structure, diversity, and demographic history of Anopheles gambiae and Anopheles arabiensis were assessed at six sites in Uganda: three islands in Lake Victoria and three mainland sites. A total of 2918 An, gambiae and 173 An. arabiensis were genotyped using targeted amplicon sequencing of 62 loci across coding and non-coding regions of the genome. Population structure analyses revealed clear separation between the two species but little differentiation within each species across sites. Pairwise FST values among An. gambiae populations were low (0.00054–0.028) but often statistically significant, with mainland populations showing higher connectivity and island populations exhibiting greater isolation. Anopheles arabiensis mainland populations showed no statistically significant differentiation, suggesting panmixia. Principal component analysis and Bayesian clustering similarly distinguished species-level structure but no obvious substructure within sites. Mainland An. gambiae populations displayed higher nucleotide diversity than island populations, while An. arabiensis showed the lowest diversity overall. Tajima’s D values were negative across sites, consistent with recent population expansions. Effective population size estimates indicated small populations at the islands (146–249) compared to large mainland populations (4054–8190). These findings demonstrate strong genetic differentiation between An. gambiae and An. arabiensis, and subtle but meaningful structure between island and mainland An. gambiae populations. The reduced diversity and small effective population sizes at island sites suggest stronger genetic drift and limited gene flow, in contrast to the highly connected mainland populations. This study highlights how geographic and ecological factors shape mosquito population structure and provides critical evidence for the design and monitoring of genetic-based vector control interventions, including the planning and evaluation of field trials.
The Genomic Arms Race in Mosquito-Borne Diseases: Integrating Entomopathogenic Fungi, Gene Drive, and Symbiont Technologies for Sustainable Vector Control
35503Rajendran Yamini, Pagalahalli Sankaran Shanmugam, Marimuthu Murugan, et al., J Pure Appl Microbiol., 20:53-65. 2026-01-20 09:32:56.
Mosquito-borne diseases such as malaria, dengue, Zika, chikungunya, and lymphatic filariasis continue to impose enormous health and economic burdens worldwide. The traditional reliance on chemical insecticides has been undermined by the rapid evolution of resistance, ecological concerns, and declining efficacy. Next-generation biocontrol strategies are framed within the concept of a “genomic arms race” between mosquitoes, pathogens, and microbial agents. Entomopathogenic fungi are eco-friendly bioinsecticides with demonstrated efficacy in laboratory, semi-field, and transgenic applications. Symbiont-based approaches, particularly those involving Wolbachia, have been evaluated for their ability to reduce vector competence and spread through populations. Parallel advances in CRISPR-based gene drive technologies have provided transformative tools for population suppression and modification, although their deployment is limited by ethical, ecological, and regulatory concerns. An integrated vector management (IVM) framework combining fungi, gene drives, and symbiont-based tools is proposed as the most promising approach for sustainable mosquito management. This multipronged strategy has the potential to reduce disease transmission, delay resistance development, and minimize ecological disruption, paving the way for resilient, eco-friendly solutions against vector-borne diseases.
Beyond the static lab: environmental variability in genetically modified mosquito target gene identification for malaria control
35371Luna Dael, Maria L. Simões, Current Opinion in Insect Science, 2026-01-17 15:23:28.
As malaria remains a critical public health challenge causing hundreds of thousands of deaths annually, novel methods to combat it are urgently needed. Genetically modified mosquitoes (GMMs) offer a promising innovative approach to reduce malaria transmission. However, the foundational research to identify the target gene candidates for genetic modification is typically conducted under static laboratory conditions. These standardized insectary settings of constant temperature and humidity do not reflect the dynamic environmental and climatic variability that mosquitoes and the pathogens they carry encounter in nature. This review argues that this “lab-to-field” discrepancy represents a significant knowledge gap. We highlight that natural variations in environmental factors influence Anopheles and Plasmodium biology, and mosquito innate immunity responses, with consequences for vector competence and malaria transmission. Insufficient consideration of environmental variability during the initial gene discovery phase risks developing GMMs where the intended function of the genetic modification may be compromised by environmental stress. We emphasize the need to incorporate realistic environmental variability into the upstream GMM development, particularly in the face of escalating climate change.
Gene drives tested against real-world malaria diversity
35377Marchal, I, Nature Biotechnology, 44. 2026-01-16 16:30:43.
Gene drive technology, which uses genetic engineering to propagate selected genes throughout a population, is a potential strategy for blocking the spread of malaria, either by suppressing mosquito populations or by making them unable to transmit the disease. However, gene drive mosquitos have mainly been tested in laboratory settings with decade-old Plasmodium parasite strains, and it is unknown whether they can block the transmission of genetically diverse Plasmodium now in circulation. In an important step toward application, Habtewold et al. now report in Nature the adaptation of a previously developed gene drive strategy to an African context.
A male-transmitted B chromosome undergoes strong meiotic drag in females of the jewel wasp Nasonia vitripennis
35373Ferree PM, Cummings J, Garman E, Solomon J, Martinez KS, PLoS Biol, 24. 2026-01-16 16:24:20.
Many organisms carry extra, non-essential chromosomes known as B chromosomes (Bs), which are selfishly transmitted at super-mendelian levels to offspring. This heightened transmission, termed drive, occurs during gametogenesis, usually in one of the two parents. In some cases, Bs can experience an opposing process, drag, which reduces their transmission. If these processes occur together in the same organism, one in each parental sex, then they may facilitate the spread of Bs while countering their accumulation in the genome to harmful levels. While previous studies have elucidated mechanistic aspects of B drive, little is known about drag or other factors that govern the inheritance of these selfish genetic elements. Here, we examined the inheritance of Paternal Sex Ratio (PSR), a single-copy B in the jewel wasp, Nasonia vitripennis, which is transmitted paternally to offspring. PSR drives by converting female-destined embryos into PSR-transmitting males. Using genetic manipulation, we produced exceptional PSR-carrying females, which were used to assess B transmission potential. We found that females transmit PSR at an unexpectedly low level compared to univalent chromosomes in other organisms. This reduced transmission stems from remarkable loss of PSR from the egg’s nucleus upon entry into meiosis, an effect that may be caused by an absence of microtubule-based spindle fibers in meiosis I-arrested wasp eggs. We also found that PSR is strictly limited to a single copy per genome, likely because wasps having two PSR copies die during development. Our findings reveal the successful inheritance of this selfish B chromosome involves its restriction to a single copy and hidden female meiotic drag in addition to strong paternal drive.
Identification and evaluation of two testis-specific serine/threonine kinase genes from multi-tissue transcriptomes as potential genetic targets of sterile insect technique in Zeugodacus tau
35439Weijun Li, Cuikang Xu, Hongshi Chen, et al., Pest Management Science, 2026-01-15 18:32:40.
Zeugodacus tau (Walker) is a notorious agricultural pest causing significant economic losses in vegetable production for many years. Sterile insect technique (SIT) has emerged as an environmentally sustainable pest management strategy. However, discovery of molecular targets applicable for SIT implementation in Z. tau still constitutes a significant research gap. We conducted comparative transcriptome analysis of four male tissues (midgut, Malpighian tubules, fat body, and testis), identifying 9653 differentially expressed genes (DEGs) with predominant testis enrichment. Bioinformatics screening revealed 3020 testis-specific highly expressed genes showing significant functional enrichment in cytoplasmic translation, cytosolic ribosome assembly, and oxidoreductase activity. Quantitative real-time PCR (qRT-PCR) assay was utilized to confirm 10 testis-specific genes, including two serine/threonine kinases (ZtTSSK1 and ZtTSSK3) which were significantly enriched in spermatid development. Fluorescence in situ hybridization (FISH) localized the two genes specifically to the transformation zone of Z. tau testis. Functional characterization via RNAi bioassay demonstrated that suppression of ZtTSSKs expression levels reduced spermatozoa number and impaired male fertility. These results establish ZtTSSKs as crucial regulators of male fertility in Z. tau and identify them as potential molecular targets for developing SIT-based interventions against this economically significant pest.
A systematic review and critical analysis of the evidence for transmission ratio distortion in humans
35379Ziyi Dai, Gregory Costain, Genetics, 2026-01-14 16:36:37.
Mendel's law of equal segregation states that during gamete formation, the 2 alleles at a gene locus segregate such that each gamete has an equal probability of containing either allele. Transmission ratio distortion (TRD) occurs when 1 of the 2 alleles from either parent is preferentially transmitted to the offspring, resulting in a deviation from the expected 1:1 ratio. Although TRD has been observed and studied in nonhuman species, the full extent and underlying biology of TRD in humans remains poorly summarized. Here we present a systematic review to assess evidence of TRD in the human genome, tracing reports from the 1970s through 2025. Overall, 96 studies including 42 different human variants/genes/loci met inclusion criteria. These studies provided only preliminary and/or conflicting evidence of TRD. Study methods were limited by multiple recurrent biases. Experimental validation of the biological mechanism(s) underlying the putative distortion was rarely performed or possible. TRD warrants renewed attention in the field of human genetics, especially with the growing availability of very large, family-based genome-wide sequencing datasets.
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.
The symbiotic Wolbachia in Anopheles and its role in reducing the transmission of Plasmodium: updates and prospects
35359Nehra, R., Dhanda, S., Singh, K. et al., Archives of Microbiology, 208. 2026-01-14 11:49:05.
Reducing malaria transmission and the prospects for vector control include multi-pronged strategies, such as interrupting the parasite cycle in both vectors and mosquitoes. Effective vector control remains essential to prevent malaria transmission. This is all the more important as problems such as resistance to insecticides and the lack of a highly effective malaria vaccine remain. New generation vector control measures and optimised products are essential to address the public health needs for malaria eradication. Strategies to reduce malaria transmission include the use of insecticide-treated nets (ITNs), indoor residual spraying (IRS) and other measures. Recent studies have shown that Wolbachia pipientis, a bacterium that acts as an intracellular endosymbiotic in host cells, is becoming increasingly popular as a new method of control for Anopheles mosquitoes, both for cytoplasmic incompatibility and for pathogen blocking. Anopheles gambiae, the infection rate ranged from 8 to 24% in the wild population of the same study in the case of An. coulzzi (WAnga) in Ghana, with a prevalence of 4%. Various studies have successfully identified Wolbachia in several species of Anopheles. A highly infected Anopheles species A population in the Democratic Republic of the Congo (DRC) showed a 91% infection rate (strain wAnsA). Broader surveys list additional species hosting natural Wolbachia, including An. funestus, An. moucheti, An. melas, An. nili, An. coustani, An. dirus, An. baimaii, An. hyrcanus, and An. sinensis, among others, totalling around 31 Anopheles species. In Anopheles stephensi, researchers achieved stable maternal transmission of the wPip strain with a 100% infection frequency in the transinfected line across generations. The infection caused nearly complete cytoplasmic incompatibility (CI) and moderate fitness costs. Previous experimental infections using the wAlbB strain in An. stephensi similarly established CI and partial protection against Plasmodium infection. Wolbachia has been detected naturally at low prevalence (~ 1.4%) in field-collected An. culicifacies samples in India. However, these infections are often rare and may not lead to a high blocking effect of the pathogens. Despite the notable progress in demonstrating the CI and moderate inhibitory effect of the pathogen in several Anopheles trans-infected lines, the remaining setbacks include persistent, mother-transmitted infection with a high population replacement or suppression potential that will be relevant for widespread use. This comprehensive evaluation identified the need for further research on host-symbiotic interactions, improved genetic engineering tools and comprehensive long-term field evaluations to fully realise the potential of Wolbachia as a vector control tool for malaria.
