Scholarly Literature
This is a database of scholarly literature that concentrates currently on natural and engineered selfish genetic elements (gene drives). The latest are shown here.
Disclaimer>
Nanobody-mediated targeting of Plasmodium falciparum PfPIMMS43 can block malaria transmission in mosquitoes
34819Ukegbu, C.V., Mohamed, M., Hoermann, A. et al., Communications Biology, 8. 2025-05-04 18:21:46.
The transition from ookinete to oocyst is a critical step in the Plasmodium falciparum lifecycle and an important target for malaria transmission-blocking strategies. PfPIMMS43, a surface protein of P. falciparum ookinetes and sporozoites, is critical for this transition and aids the parasite in evading mosquito immune responses. Previous studies demonstrated that polyclonal PfPIMMS43 antibodies reduced P. falciparum infection in Anopheles mosquitoes. Here, building on these findings, we have developed high-affinity single-domain VHH antibodies (nanobodies) derived from llama heavy-chain-only antibodies. We have shown that these nanobodies bind both recombinant and endogenous PfPIMMS43 produced by P. falciparum ookinetes in the mosquito midgut. Importantly, they significantly reduce infection intensity and prevalence of laboratory and field strains of P. falciparum in An. coluzzii and An. gambiae, respectively. Epitope mapping has revealed that the nanobodies target conserved regions in the second half of PfPIMMS43, with homology modelling confirming epitope accessibility. These findings establish PfPIMMS43 as a promising transmission-blocking target. To enhance malaria control and elimination efforts, we propose an innovative strategy in which genetically modified mosquitoes express PfPIMMS43-specific nanobodies in their midguts and spread this trait in wild mosquito populations via gene drive technology.
Maximising Eradication Potential of Rat Gene Drives Using a Two-Target Homing Rescue Strategy: Spatial Modelling of Empirical Data
34817Birand, A., Gierus, L., Prowse, T., Cassey, P., Thomas, P.Q., Molecular Ecology, 2025-05-04 16:12:38.
Gene drives are genetic elements with positively biased transmission and may be useful tools to suppress mammalian pests that threaten biodiversity worldwide. While gene drives are progressing in mice, less is known about their potential for invasive rat control. A recent report has provided the first data on germline gene conversion in rats, demonstrating that modest homing rates (up to 67%) can be achieved in females. Here, we apply these empirically derived values to investigate the potential of various gene drive strategies to suppress an island population of 200,000 rats, using our stochastic, spatially explicit, individual-based modelling framework. Standard homing drives embedded in haplosufficient fertility or viability genes failed to eradicate, but achieved permanent population suppression. In contrast, a two-target design with a homing rescue (HR) drive embedded in a haplolethal gene that also targets an independent fertility or viability gene demonstrated considerable suppression potential. Remarkably, an HR drive targeting a haplosufficient female fertility gene showed robust eradication even at the relatively low homing rates previously demonstrated in rats. Interestingly, homing rate had a relatively low influence on eradication probability while cutting efficiency at the haplolethal gene was critical. Further, as long as the latter was similar to the cutting and subsequent knockout of the unlinked female fertility gene, then eradication could be achieved across a range of homing rates. Together, these results suggest that modest homing rates, such as have been demonstrated in rats and other species, can potentially be leveraged for population suppression, offering new opportunities for gene drive development.
Impact of sterile Aedes aegypti males releases on vector dynamics: insights from Malaysian field trials
34815Nazni, W.A., Teoh, GN., Nuradila, M.A. et al., Infectious Diseases of Poverty, 14. 2025-05-04 16:00:48.
The Sterile insect technique (SIT) has been successfully used in agricultural pest control, leading to interest in its application for public health, particularly in controlling Aedes mosquitoes in the USA, Italy, Cuba, and Greece. Malaysia has conducted a small-scale SIT pilot trial since 2019 for dengue control. This study evaluates mosquito populations in treated and untreated sites through three objectives: (1) comparing mean larvae per trap (MLT) and dengue cases for Ae. aegypti and Aedes albopictus; (2) estimating survival rates and wild populations using mark-release-recapture (MRR); and (3) analysing spatial distribution in treated and untreated sites. Ae. aegypti males, irradiated at 55 Gray, were released in three locations: Pangsapuri Kota Laksamana (KT), Malacca (19 months), Pangsapuri Taman Tasik Utama (TTU), Malacca (8 months), and the Customs, Immigration, and Quarantine Complex (CIQ), Johor (7 months). Statistical analyses assessed SIT effectiveness, including T-tests for larval density and ovitrap indices, Mulla’s formula and relative variance (RV) for population reduction, and the Lincoln Index for estimating wild male populations and probability of daily survival. Weekly releases of sterile Ae. aegypti males at doses of 1278–7942 males/ha achieved a sterile-to-wild male ratio of 5.85 and a mean daily survival rate of 0.61, leading to significant reductions in larval densities: 76.25% in Kota Laksamana (KT), 96.74% in Taman Tasik Utama (TTU), and 89.00% in CIQ Gelang Patah, thereby supporting dengue control efforts. In KT, the MLT was initially low but increased, although with suppression < 90%, there was a reduce of dengue cases throughout the release period. The MRR’s mean survival rate (± standard deviation) in KT was 0.61 (± 0.08). The spatial clustering of Ae. aegypti was observed in central blocks during the high MLT period. However, larval densities rebounded after releases ceased. Spatial clustering revealed no initial clustering, though clustering patterns emerged over time in KT. SIT effectively suppressed Ae. aegypti populations and supported dengue control. Optimizing sterile-to-wild male ratios, spatial distribution, and monitoring strategies is essential for sustainable vector control. These findings provide insights for scaling up SIT field trials, with future efforts focusing on refining release and monitoring strategies to enhance SIT as an effective dengue control tool. Trial registration NMRR-17–2652-39,099 “Field evaluation of Sterile Insect for Aedes aegypti Suppression.”
Economic evaluation of Wolbachia deployment in Colombia: A modeling study
34812Shepard, D.S., Lee, S.R., Halasa-Rappel, Y.A., Rincon Perez, C.W., Harker Roa, A., PLoS One, 20. 2025-05-04 15:55:06.
Wolbachia are bacteria that inhibit dengue virus replication within the mosquito. A cluster-randomized trial in Indonesia found Wolbachia reduced virologically-confirmed dengue cases by 77.1%. Previous models predicted Wolbachia to be highly cost-effective in Indonesia, Vietnam, and Brazil. To inform decisions about future extensions in Colombia, we performed economic evaluations of potential Wolbachia deployments in 11 target cities. We assembled the numbers and distribution by severity of reported dengue cases from Colombia’s national disease surveillance system and the health service provision registry (RIPS). An epidemiological panel of three experts estimated the shares of dengue that were non-medical, under-reported, or misreported as another disease. We determined costs (in 2020 US dollars at market prices) of treating dengue illness from the benchmark insurance tariff and RIPS data on treatment services per symptomatic dengue case. Our central estimates projected 10 years of efficacy and focused on Cali, the target city with the highest number of dengue cases. For Cali, we estimated a net health-sector savings of US$4.95 per person and averting 369 disability-adjusted life years (DALYs) per 100,000 population. From a societal perspective, at 10 years Wolbachia deployment is expected to have highly favorable benefit-cost ratios, with benefits per dollar invested of US$5.50 in Cali and US$4.68 over all target cities. Over 10 years, Wolbachia is highly beneficial on economic grounds, and almost universally cost saving. The Wolbachia program’s economic benefits exceeded its costs in all 11 cities. The program’s savings in healthcare costs alone would more than offset deployment costs nationally and in 9 of 11 target cities. Wolbachia is likely to be the most cost-effective or cost-saving dengue control option in municipalities with both high incidence of dengue and high population density, whereas areas with high dengue incidence but low population density should consider vaccination.
Optimizing Cost-Effective Larval Diets for Mass Rearing of Aedes Mosquitoes in Vector Control Programs
34810Li, Q., Wei, T., Sun, Y., Khan, J., & Zhang, D., Insects, 16. 2025-05-04 15:43:50.
Larval diet composition significantly influences the developmental, physiological, and reproductive traits of Ae. albopictus and Ae. aegypti, major arbovirus vectors. Optimizing larval nutrition is essential for mass-rearing programs supporting the sterile insect technique and incompatible insect technique. This study evaluated the effects of three larval diets on key fitness traits, including pupation rate, male flight ability, adult longevity, female fecundity, pupal size, and wing length, which are critical for the success of SIT and IIT programs. (2) Methods: Ae. albopictus (GT strain) and Ae. aegypti (AEG strain) were reared on three diets with varying protein sources: diet 1 (≈1.23 dollars/kg; porcine liver/shrimp/yeast = 6:3:1), the IAEA-recommended diet; diet 2 (≈1.78 dollars/kg; bovine liver/shrimp/yeast = 6:3:1), a modified IAEA diet; and diet 3 (≈0.55 dollars/kg; tortoise food), a low-cost laboratory formulation. Life history traits were assessed using standardized protocols, and data were analyzed with ANOVA and Tukey’s post hoc test. (3) Results: Diet 3 consistently improved pupation rates, adult longevity, and male flight ability compared with diet 2. Mosquitoes reared on diets 1 and 3 exhibited significantly larger pupae and longer wings, while diet 2 performed sub-optimally. Adult eclosion rates (~100%) remained high across all diets. Male flight ability varied by species, with Ae. albopictus performing best on diet 1 and Ae. aegypti on diet 3. Female fecundity was diet-dependent, with diet 1 favoring Ae. albopictus and diet 3 benefitting Ae. aegypti. Longevity was highest in mosquitoes reared on diet 3, with a median survival of 19.5 days for GT males and 37.5 days for GT females. (4) Conclusions: Diet 3 emerged as the most cost-effective option, enhancing key fitness traits essential for SIT and IIT. Future studies should refine nutrient formulations and validate findings under field conditions to optimize mass-rearing efficiency in vector control.
A selfish supergene causes meiotic drive through both sexes in Drosophila
34805G.L. Keais,C.M. Saad-Roy,E. Gonzalez-Sqalli, et al., Proceedings of the National Academy of Sciences, 122. 2025-04-25 12:15:11.
Meiotic drivers are selfish genetic elements that bias their own transmission during meiosis or gamete formation. Due to the fundamental differences between male and female meiosis in animals and plants, meiotic drivers operate through distinct mechanisms in the two sexes: In females, they exploit the asymmetry of meiosis to ensure their inclusion in the egg, whereas in males, they eliminate competing gametes after symmetric meiosis. Meiotic drive is commonly reported in males, where it strongly influences the evolution of spermatogenesis, while the few known cases in females have highlighted its crucial role in centromere evolution. Despite a growing number of examples in a wide range of organisms, meiotic drive has so far only been observed in one sex or the other since its discovery nearly 100 y ago. Here, we show that a selfish X chromosome known to cause meiotic drive in male Drosophila testacea flies also causes meiotic drive in females. We find that this X chromosome has supergene architecture, harboring extensive structural rearrangements that suppress recombination between the two X chromosomes. This has contributed to a substantial expansion of its size compared to the wild-type chromosome, partly due to the accumulation of species-specific repetitive elements. Our findings suggest that female meiotic drive may play an important role in the evolutionary dynamics of polymorphic structural variants that suppress recombination, including inversions, translocations, and supergenes.
Optimization of SgRNA expression with RNA pol III regulatory elements in Anopheles stephensi
34801Gonzalez, E., Anderson, M.A.E., Ang, J.X.D. et al., Scientific Reports, 15. 2025-04-23 11:08:06.
Anopheles stephensi, a major Asian malaria vector, is invading Africa and has been implicated in recent outbreaks of urban malaria. Control of this species is key to eliminating malaria in Africa. Genetic control strategies, and CRISPR/Cas9-based gene drives are emerging as promising species-specific, environmentally friendly, scalable, affordable methods for pest control. To implement these strategies, a key parameter to optimize for high efficiency is the spatiotemporal control of Cas9 and the gRNA. Here, we assessed the ability of four RNA Pol III promoters to bias the inheritance of a gene drive element inserted into the cd gene of An. stephensi. We determined the homing efficiency and examined eye phenotype as a proxy for non-homologous end joining (NHEJ) events in somatic tissue. We found all four promoters to be active, with mean inheritance rates up to 99.8%. We found a strong effect of the Cas9-bearing grandparent (grandparent genotype), likely due to maternally deposited Cas9.
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.
An eco-epidemiological model for malaria with Microsporidia MB as bio-control agent
34793Mfangnia CNT, Tonnang HEZ, Tsanou B, Keith Herren J, Modeling Earth Systems and Environment, 11. 2025-04-23 10:24:11.
Microsporidia MB is an endosymbiont which naturally infects Anopheles mosquitoes. Due to its ability to block Plasmodium transmission, it shows potential as a bio-based agent for the control of malaria. Its self-sustainability is promising, as it can spread through both vertical and horizontal transmissions. However, its low prevalence in mosquito populations remains a challenge. We develop an eco-epidemiological mathematical model describing the co-dynamics of Microsporidia MB (within mosquito population) and malaria (within human population). The model is used to assess the potential of Microsporidia MB-infected mosquitoes on the control of malaria infection. The results on the basic reproduction numbers, the stability of the equilibria, and the existence of bifurcations are obtained, providing conditions for the extinction and persistence of MB-infected mosquitoes. We highlight relevant threshold parameters for the elimination and persistence of MB-infected mosquitoes and malaria-infected individuals. Using real data from Kenya, we found that, given a horizontal transmission rate between 0 and 0.5, a minimum vertical rate of 0.55 is required to avoid extinction of MB-infected mosquitoes. The predicted prevalence of MB-infected mosquitoes using transmission rates reported from lab experiments align with the observed low prevalence of MB-infected mosquitoes in the field, thereby validating our model and results. Finally, predictions indicate that increasing MB mosquito infection could effectively control malaria, with target prevalence varying by region: 15% in Highland, 40% on the coast, and 70% in the Lake region. This study offers insights into the use of bio-based vector population replacement solutions to reduce malaria incidence in regions where Microsporidia MB is prevalent.
International perspectives on the meaning of engagement in biotechnology risk assessment: the case of gene drive
34789Hartley, S., Stelmach, A., Kokotovich, A., & Smith, R. D. J., Journal of Risk Research, 2025-04-23 10:10:43.
Biotechnology remains challenging for risk assessors. The risk assessment of genetically modified organisms was the locus of considerable, acrimonious, and politicised debate and subjected to intense scrutiny. Since then, biotechnology has evolved to include new tools, such as genome editing and gene drive, and risk assessors are more sensitive to stakeholder and public views. While engagement is increasingly recognised as important in risk governance, it is underrepresented in the governance literature, remains challenging in risk assessment, and needs empirical cases to develop theory. Imagining engagement in risk assessment will require thinking about when, where, and how to engage people in risk assessment processes in both research and regulatory contexts. However, current risk assessment methods and processes make engagement of non-technical experts challenging and risk assessors may need to innovate and diverge from the norms of risk assessment. Gene drive presents a case of risk assessment that has generated a plethora of prescriptive calls and recommendations for engagement. We use this case study to explore how both technical and non-technical experts and stakeholders involved in gene drive risk assessment are imagining engagement. We conduct qualitative, interpretive research, drawing on 30 interviews with participants across five continents. We show that the people involved with engagement in risk assessment are talking about drastically different things when they talk about engagement. Placing an empirical and theoretical spotlight on engagement in risk assessment, we argue that conversations need to draw on our insights to move beyond simply recognising, justifying, and calling for engagement.
Mathematically modelling the population dynamics of CRISPR gene drive systems in the pine pest Sirex noctilio
34779Strydom, H., Ouifki, R., Chapwanya, M., bioRxiv, 2025-04-18 10:34:17.
Sirex noctilio is an invasive pest of pine that has caused significant economic damage in South Africa and many other Southern Hemisphere countries. Current management tools are not efficient in all cases and consequently there is a need for more efficient and targeted control measures. An emerging tool for pest management is the use of gene editing and associated gene drive systems. In this study, we aim to investigate the use of CRISPR-Cas gene drive systems in the management of S. noctilio in South Africa. As a first step, we developed a model for the population dynamics of S. noctilio, using historical national population monitoring data and incorporating the influence of two main biological control agents of the pest. We then modelled the influence of two different CRISPR-Cas systems on the population dynamics of S. noctilio namely, a baseline CRISPR model and Complementary Sex Determination CRISPR (CSD) model. Each model is used to simulate a male and female only introduction strategy to estimate the effectiveness of different methods of introducing the gene drive system. The model calibration was achieved by optimizing the model fit to existing data using the least squares technique. Results suggest that both CRISPR gene drive systems would be effective at controlling the population growth of S. noctilio at high levels of introduction, but overall population control would be hindered by practical limitations. Although only two CRISPR models were explored, the underlying population model serves as a framework for further studies into the population dynamics of Sirex noctilio, as well as many other CRISPR-Cas gene drive systems.
Evolutionary consequences of long-distance dispersal in mosquitoes
34776Thomas L Schmidt, Current Opinion in Insect Science, 68. 2025-04-18 10:25:09.
Long-distance dispersal (LDD) provides a means for mosquitoes to invade new regions and spread adaptive alleles, including those conferring insecticide resistance. Most LDD takes place on human transport vessels and will typically be rarer and more directionally constrained than active flight but can connect populations and regions that are otherwise mutually inaccessible. These features make LDD worthy of specific consideration in mosquito research. This paper reviews recent evolutionary research on LDD and its consequences for mosquito populations and mosquito control. LDD is the main source of mosquito range expansions, and genomic methods can now trace the origins of new invasions to specific towns or cities. Genomic methods can also give a rough indication of the number of invaders, which if very small may lead to the stochastic loss of advantageous alleles during invasion bottlenecks. Once invasions are established, LDD spreads adaptive alleles between populations. Emerging insights into insecticide resistance evolution indicate that LDD has repeatedly spread resistance mutations across global species ranges, but these broad patterns are convoluted by two other evolutionary processes: parallel adaptation at the same gene or gene cluster and polygenic adaptation at different genes in different populations. Together, these processes have produced patterns of similarity and dissimilarity at resistance genes that are decoupled from geographical distance. LDD within cities is less well studied but is important for planning and evaluating local control efforts. Urban investigations of LDD may help identify areas experiencing weaker selection pressures from insecticides and isolated areas to target for control.
Applications and status of gene drive in plants
34771Hay BA, PLOS Biology, 23. 2025-04-18 10:06:07.
Globalization—the movement of humans, plants, animals, and microbes—together with climate change, place numerous plant and animal species under novel stresses. For plants, threats include global warming, invasive species, weeds, animal pests, and vectors of disease. Harms can be mitigated or prevented through population-scale genetic alterations that introduce beneficial traits such as disease resistance or drought tolerance (population modification), or that eliminate a harmful population (population suppression). Gene drive is a possible tool for achieving these goals. DNA mediating gene drive comprises one or more genes (the drive element) that promote their own inheritance—and any linked cargo—at rates exceeding (>50%) those of other genes. This can lead to an increase in drive element frequency even if its presence results in a fitness cost to carriers. Gene drive is attractive because it is self-amplifying and self-sustaining. One class of gene drive utilizes a Toxin-Antidote (TA) element. In nature, these often consist of two tightly linked protein-encoding genes. One encodes a toxin that is inherited by all gametes and/or progeny of a carrier; the second is an antidote that protects carriers from death. The TA element-bearing chromosome gains a relative transmission advantage by causing death of those who fail to inherit it. The first synthetic gene drive was engineered using TA logic, in Drosophila melanogaster in 2007. Recently, TA logic was also used to create the first synthetic gene drive elements in plants, in Arabidopsis thaliana. These use a Cleave and Rescue mechanism (ClvR) adapted from earlier work in Drosophila. ClvR uses DNA cleavage mediated by Cas9 and guide RNAs (gRNAs), followed by inaccurate repair, to create loss-of-function (LOF) alleles (the toxin) of endogenous versions of an essential gene. ClvR also includes a Rescue version of the essential gene recoded to prevent gene disruption (the antidote), which guarantees survival of carriers. In Drosophila, ClvR spreads because LOF alleles created in parents cause the death of progeny who lack essential gene function. In Arabidopsis this strategy was used to create gamete killers. A naturally occurring male gamete killer from rice, DUYAO-JIEYAO, consists of a two-gene protein–protein TA cassette. Modeling suggests that gamete killers such as these can bring about population modification or suppression. Interestingly, the DUYAO-JIEYAO element has undergone a substantial increase in frequency in Japonica rice populations in China over the last 50 years, demonstrating the power of such elements in nature.
Problem formulation for a small-scale field study of non-gene drive, genetically modified, male bias mosquitoes in Burkina Faso
34758Hayes, K. R., & Hosack, G. R., Human and Ecological Risk Assessment: An International Journal, 2025-04-10 09:17:32.
This article documents the problem formulation step of a risk assessment for a proposed small-scale field release in Burkina Faso of genetically modified (GM) An. coluzzii mosquitoes that carry a Paternal Male Bias (PMB) construct. These mosquitoes are part of the pathway developed by Target Malaria to provide a new cost-effective control strategy for malaria vectors in Africa. The problem formulation describes 7 potentially harmful outcomes that might occur through 19 pathways to harm and identifies 22 types of desk-based analysis, 6 laboratory tests, and 5 field observations that can be used to test the risk hypotheses associated with these pathways. The problem formulation forms the basis of a prerelease risk assessment that meets the standards stipulated under the Cartagena Protocol and guidance provided by the World Health Organization, the African Union Development Authority, and the European Food Safety Authority. The Problem Formulation reflects the concerns expressed about the proposed field release by relevant stakeholders, although stated concerns are not always specific enough to be unambiguously associated to a single pathway. The presentation of the pathways to harm emphasizes the types of evidence that supports the steps within each pathway, and so portrays the speculative nature of some pathways.
Synthetic Homing Endonuclease Gene Drives to Revolutionise Aedes aegypti Biocontrol – Game Changer or Pipe Dream?
34756Joshua X.D. Ang, Sebald A.N. Verkuijl, Michelle A.E. Anderson, Luke Alphey, Current Opinion in Insect Science, 2025-04-10 09:10:46.
The increasing burden of Aedes aegypti-borne diseases, particularly dengue, is a growing global concern, further exacerbated by climate change. Current control strategies have proven insufficient, necessitating novel approaches. Synthetic homing endonuclease gene (sHEG) drives represent one of the few emerging technologies with the potential to offer a cost-effective and equitable solution to this escalating public health challenge. However, despite multiple attempts, the homing efficiencies of Ae. aegypti sHEG systems lag behind those achieved in Anopheles mosquitoes. We discuss key insights from efforts to develop sHEGs in Ae. aegypti and highlight critical factors that may unlock further advances in this species.
An innovation in host responses to escalating genomic conflicts
34753Martí, Emiliano et al., Trends in Genetics, 2025-04-07 12:54:24.
Conflicts between selfish elements and their hosts can trigger rapid structural and regulatory changes in genomes. Chen et al. discovered a novel species-specific innovation in response to a meiotic driver in Drosophila melanogaster. Their discovery highlights a new dimension in adaptive responses to selfish elements, with broad evolutionary consequences.
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.
Wolbachia: A bacterial weapon against dengue fever- a narrative review of risk factors for dengue fever outbreaks
34743Safaei, S., Derakhshan-Sefidi, M., Karimi, A., New Microbes and New Infections, 65. 2025-04-04 14:53:55.
Arboviruses constitute the largest known group of viruses and are responsible for various infections that impose significant socioeconomic burdens worldwide, particularly due to their link with insect-borne diseases. The increasing incidence of dengue fever in non-endemic regions underscores the urgent need for innovative strategies to combat this public health threat. Wolbachia, a bacterium, presents a promising biological control method against mosquito vectors, offering a novel approach to managing dengue fever. We systematically investigated biomedical databases (PubMed, Web of Science, Google Scholar, Science Direct, and Embase) using “AND” as a Boolean operator with keywords such as “dengue fever,” “dengue virus,” “risk factors,” “Wolbachia,” and “outbreak.” We prioritized articles that offered significant insights into the risk factors contributing to the outbreak of dengue fever and provided an overview of Wolbachia's characteristics and functions in disease management, considering studies published until December 25, 2024. Field experiments have shown that introducing Wolbachia-infected mosquitoes can effectively reduce mosquito populations and lower dengue transmission rates, signifying its potential as a practical approach for controlling this disease.
Comparison of oviposition and adult trapping to monitor wMel introgression for Wolbachia-based vector control
34738Nelson, E., Pereira, T.N., Ribeiro E., et al., bioRxiv, 2025-04-03 17:36:42.
Wolbachia introgression into Aedes aegypti mosquito populations has been shown to be effective in preventing dengue and is being evaluated for WHO prequalification. Monitoring the long-term introgression of Wolbachia (wMel)-positive Aedes aegypti mosquitoes, however, requires labor-intensive and costly BG-Sentinel traps (BG-traps). More affordable alternatives, such as using oviposition traps (ovitraps), have not been fully evaluated. Ae. aegypti eggs and adults were collected from 124 ovitraps and 237 BG-traps, respectively, across 12 clusters in Belo Horizonte, Brazil from March to May 2023 as part of the EVITA Dengue trial. We used a qPCR assay to detect wMel in a sample of L3-L4 stage larvae (up to 29) that were reared from eggs in ovitraps and adults from BG-traps (up to 10 per BG-trap). We used mixed effects models to compare estimates of cluster-level wMel introgression from ovitrap and BG-trap data over time. Among 3,675 larvae reared from ovitraps, wMel prevalence was 0.50 (95% CI: 0.48-0.51). Among 1,244 adult Ae. aegypti tested from BG-traps, wMel prevalence was 0.45 (95% CI: 0.42-0.48). Cluster-level wMel introgression in larvae and adults was highly correlated (Spearman’s r = 0.70, p = 6.71e-06). Multivariate analysis found that ovitrap estimates of introgression were associated with BG-trap estimates in the same month when models incorporated the previous month’s ovitrap wMel-positive count, the proportion of wMel in ovitraps in the current and previous month, and Ae. aegypti abundance. Leveraging this model, predicted wMel introgression from ovitrap data were highly correlated with observed introgression from BG-trap data (rs,counts=0.98, p=1.53e-14; rs,prevalences=0.82, p=0.11e-05) and provided greater precision than crude ovitrap-based estimates.
Mosquito Sex Separation using Complementation of Selectable Traits and Engineered Neo-Sex Chromosomes
34736Zaada, D.S.Y., Toren, O., Krsticevic, F., et al., bioRxiv, 2025-04-03 17:26:54.
Effective and scalable sex separation remains a critical challenge for mosquito genetic control strategies. Genetic sexing strains (GSS) address this by genetically linking maleness with selectable traits, enabling efficient removal of females before release. Here, we describe a robust platform for the development of GSSs in the invasive Aedes albopictus mosquito by integrating a CRISPR-engineered selectable phenotype with sex conversion via nix, the male-determining factor. As a proof-of-concept, we disrupt the yellow gene to generate a vivid pigmentation marker, then rescue its function in males using nix-containing transgenes, creating a stable strain where all females are yellow and all engineered males are dark. The resulting GSS males are fertile, robust, and despite lacking the ancestral M locus, exhibit gene expression profiles closely resembling wild-type males. We benchmark sex separation based on pigmentation and discover that yellow mutant females exhibit slower larval development, enhancing protandry-based sorting. The GSS strain is compatible with existing size-based sex sorting systems, allowing for improved separation accuracy through the integration of natural and engineered sexually dimorphic traits. Additionally, we find that GSS females lay desiccation-sensitive eggs, reducing the risk of accidental female releases. Our approach is the first to engineer a sex-linked selectable trait by precisely targeting an endogenous gene and restoring its function in males, establishing a versatile platform for GSS development in Aedes mosquitoes.

Contact Us
Alex Sullivan
Foundation for the
National Institutes of Health
geneconvenevi@fnih.org
