Peer-reviewed publication2026-Jul-02
Invasive rodents are major contributors to biodiversity loss, particularly on islands where native species have evolved in their absence. Genetic biocontrol offers a promising suite of species-specific technologies that may contribute to rodent suppression and elimination. Here, we evaluate the potential of Y-linked genome editors (YLEs), which contain a nuclease that disrupts a female-essential fertility or viability gene, to suppress or eliminate a mouse population on a small, isolated island. We use the MouseGD simulation framework to model the inheritance patterns of YLEs and other genetic biocontrol tools in the context of rodent life history, calculating elimination probabilities, times to elimination and other outcomes for a range of construct and release parameters. Simulations suggest that YLEs are more efficient than other self-limiting tools, and are capable of achieving elimination within a short timeframe for modest release sizes. For an in silico mouse population size of 10,000, elimination is simulated within 5 years for releases of 350 males per month, and within 10 years for releases of 150 males per month. This scale of production is within existing capabilities, potentially enabling suppression to encompass a larger spatial scale. Simulations suggest that elimination could be achieved for YLEs targeting both haploinsufficient and haplosufficient target genes. Gene drives were simulated to achieve suppression and elimination for smaller release sizes; but also to spread to non-target populations. In contrast, YLEs display minimal spillover. These characteristics present YLEs as a promising, ecologically manageable biocontrol tool for elimination of invasive rodents and conservation of native species.
Gene drives
Peer-reviewed publication2026-Jan-20
Mosquito-borne disease and nuisance biting from mosquitoes have severe health and economic consequences. Conventional fabrics are typically not effective at providing protection against mosquito bites, and fabrics treated with repellents and/or insecticides are limited by rising insecticide resistance, risk of significant dermatologic and neurologic side effects, and decreased efficacy with washing and time. The goal of this study was to identify commercially available, repellent/insecticide-free, comfortable fabrics that block bites from three genera of mosquitoes that are known to transmit dangerous infectious diseases with widespread distribution: Aedes, Anopheles, and Culex. To do this, we evaluated fabrics from Ripstop By the Roll LLC in a step-wise series of mouse blood-feeding and behavioral bioassays. Out of 88 fabrics, 53 were found to be blood-feed-proof. These fabrics were more likely to have a higher areal weight density (AWD) and a polyurethane coating than blood-feed-susceptible fabrics. Of the six most comfortable fabrics by subjective hand-feel testing, five were definitively bite-proof during behavioral bioassays. These five fabrics varied substantially in AWD, thickness, finish/coating, and fiber pattern. None of them had a polyurethane coating. Three of them were breathable, making them appropriate for active-wear clothing. Overall, the bite-proof fabrics identified in this study have the potential to significantly reduce mosquito biting and the transmission of mosquito-borne diseases.
Mosquito biologyAnopheles
Peer-reviewed publication2026-Jan-15
The recent discovery of the type III-E class of CRISPR-Cas effectors has reshaped our fundamental understanding of CRISPR-Cas evolution and classification. Type III-E effectors are composed of several Cas7-like domains and a single Cas11-like domain naturally fused together to create a single polypeptide capable of targeting and degrading RNA. Here we identified a novel type III-E-like effector composed of three Cas7 domains and a Cas1 domain which was not active but could be engineered into an active chimeric RNA-targeting Cas effector by domain additions and swaps from other type III-E effectors. The results reveal that various domains in type III-E effectors can be swapped for the equivalent domain from a different type III-E effector. Remarkably, the Cas1 domain located at the C-terminus of Cas7-1 could be swapped in place of the Cas11 domain located between the Cas7.1 and the Cas7.2 domains of DiCas7-11. The results reveal a new modality for engineering type III-E effectors from the blueprints found in nature.
Genome engineering
Peer-reviewed publication2026-Feb-20
Plant-derived repellents containing borneol and camphor have been used for centuries, yet the sensory mechanisms that mediate their effects in mosquitoes have remained obscure. Here, we show that culicine mosquitoes possess a dedicated olfactory pathway for detecting bicyclic monoterpenoids. We identify odorant receptor 49 (OR49) as a conserved and highly selective borneol receptor expressed in a distinct neuron of the maxillary palp. This neuron forms a defined projection to the MD3 glomerulus in the antennal lobe, establishing a labeled line for plant-derived repellents. Genetic disruption of Or49 abolishes electrophysiological responses to borneol and markedly diminishes avoidance behavior during human host-seeking. These results reveal that female mosquitoes detect borneol through a specialized sensory channel distinct from those mediating attraction to human cues. Our findings provide a mechanistic framework for understanding how plant volatiles shape mosquito behavior and offer a foundation for the rational design of next-generation olfactory repellents.
Mosquito neurobiologyMosquitoes
Peer-reviewed publication2026-Feb-05
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.
Sterile insect techniques
Peer-reviewed publication2026-Aug-13
No summary is available.
Other
Peer-reviewed publication2026-Aug-05
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.
Gene drives
Peer-reviewed publication2026-Apr-10
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.
Gene drivesMosquitoes
bioRxiv preprint2026-09-18Not peer reviewed
Mosquito-borne pathogens cause approximately 700,000 deaths annually, highlighting the need for effective and sustainable vector control strategies. CRISPR-based gene drives offer a potential approach for suppressing disease-vector populations, but autonomous drives may spread beyond intended populations. Split gene drives, in which the Cas9 and guide RNA components are genetically separated, provide an inherently confinable alternative because biased inheritance depends on the co-occurrence of both components. Here, we develop the first split suppression gene drives in Ae. aegypti, targeting the female reproductive genes doublesex (dsx) and yellow-g (yg). The yg-targeting drive exhibited moderate super-Mendelian inheritance, reaching 73.4% transmission in the highest-performing cross, whereas the dsx-targeting drive exhibited little detectable inheritance bias. Conversely, disruption of dsx imposed substantially stronger reproductive fitness costs, including complete sterility in homozygous females, whereas yg disruption produced a less severe fertility phenotype. Mathematical modeling parameterized with these experimental data predicted that three of four split-drive configurations could achieve population suppression at lower release intensities or shorter release durations than pgSIT across portions of the modeled parameter space. Together, these results reveal that inheritance efficiency and reproductive load can impose competing constraints on split suppression drive performance: stronger suppression-associated fitness effects do not necessarily translate into improved drive performance when accompanied by limited drive propagation. Our findings establish the feasibility of split suppression gene drives in Ae. aegypti and demonstrate that effective suppression drive design requires balancing inheritance efficiency with reproductive fitness costs rather than maximizing either independently.
Sterile insect techniquesAedes
bioRxiv preprint2026-09-03Not peer reviewed
The acoustic communication system supporting reproduction in disease-transmitting mosquitoes is sexually dimorphic, from the sounds that mosquitoes make to the properties of their flagellar ears. The molecular mechanisms shaping these dimorphisms, however, remain unclear. Here, we explored the contributions of the female-specific isoform of the sex determination gene doublesex ( dsxF ) in specifying female-unique properties in the acoustic communication system of Aedes aegypti mosquitoes. CRISPR-Cas9 based generation of a novel dsxF knockout line found that dsxF mutant females were flightless due to lack of expression of a female-specific myosin gene, myo-fem , in the thorax. We found that DsxF directly binds to four different enhancer sites of myo-fem to promote gene expression. We observed that dsxF female ears exhibited intersex neuroanatomical characteristics and contained a more extensive auditory efferent network than control females. At the peripheral hearing function level, dsxF female ears displayed intersex tuning frequencies associated with increased expression of hearing genes in dsxF female ears compared to control females. We identified three hearing genes transcriptionally inhibited by DsxF via direct binding. DsxF is a bifunctional transcription factor, activating female-specific gene expression in thoraces whilst repressing male-biased gene expression in ears to coordinate female-unique features across sensory and motor systems.
Mosquito biologyAedes
Institutional or lab press2026-09
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Institutional or lab press2026-08
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Institutional or lab press2026-07
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Institutional or lab press2026-06
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Institutional or lab press2026-05
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Institutional or lab press2026-03
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Institutional or lab press2026-02
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Institutional or lab press2026-01
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Peer-reviewed publication2026
Chemical insecticides have long been used to control agricultural pests, but their widespread application has driven resistance and caused significant ecological and health impacts. CRISPR/Cas9-based genetic biocontrol technologies, including the precision-guided sterile insect technique (pgSIT) and homing gene drives (HGDs), offer targeted alternatives for suppressing pest populations with reduced environmental cost. pgSIT produces sterile males without radiation and achieves high mating competitiveness without multigenerational persistence. In contrast, HGDs bias inheritance to enable sustained population suppression through disruption of essential fertility or viability genes, albeit with greater ecological and regulatory considerations. Experimental applications in multiple agricultural pest species demonstrate robust suppression efficacy. Emerging innovations, including temperature-inducible pgSIT systems, may further streamline mass-rearing and deployment. Together, these approaches have the potential to reduce crop losses and reliance on chemical insecticides while lowering long-term management costs. Their successful integration into agricultural systems will depend on rigorous risk assessment, regulatory oversight, and stakeholder engagement.
Sterile insect techniques
Peer-reviewed publication2025-Sep-3
Malaria control has primarily been achieved through vector control, but current methods are insufficient to achieve elimination. Precision guided sterile insect technique (pgSIT) is a mosquito suppression technique that generates sterile male mosquitoes for mass release. Our previous studies showed that this intervention is expected to be highly cost-effective in a malaria endemic region of West Africa, but these estimates used only 15-31% capacity for sex sorting, which is the limiting production step and a primary cost. We, therefore, determined the most cost efficient facility size by calculating the cost per million Anopheles gambiae suppressed as the facility was scaled up to suppress more mosquitoes. We developed an optimized facility size per 9.2 million mosquitoes suppressed, which can be a framework for scaling and increases the cost effectiveness of this intervention. The development of this intervention can potentially interrupt malaria transmission, strengthen local public health institutions, create manufacturing capacity, provide local jobs, and enhance regional health security capabilities that are more resilient to disruptions in supply chains and malaria investment.
Sterile insect techniquesAnopheles