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.
Hybrid mosquitoes? Evidence from rural Tanzania on how local communities conceptualize and respond to modified mosquitoes as a tool for malaria control
16567M. F. Finda, F. O. Okumu, E. Minja, R. Njalambaha, W. Mponzi, B. B. Tarimo, P. Chaki, J. Lezaun, A. H. Kelly and N. Christofides, Malaria Journal, 20:134. 2021-03-06 14:11:52.
Different forms of mosquito modifications are being considered as potential high-impact and low-cost tools for future malaria control in Africa. Although still under evaluation, the eventual success of these technologies will require high-level public acceptance. Understanding prevailing community perceptions of mosquito modification is, therefore, crucial for effective design and implementation of these interventions. This study investigated community perceptions regarding genetically-modified mosquitoes (GMMs) and their potential for malaria control in Tanzanian villages where no research or campaign for such technologies has yet been undertaken.
A confinable home and rescue gene drive for population modification
16579N. P. Kandul, J. Liu, J. B. Bennett, J. M. Marshall and O. S. Akbari, eLife, 10:e65939. 2021-03-05 16:30:16.
Homing based gene drives, engineered using CRISPR/Cas9, have been proposed to spread desirable genes throughout populations. However, invasion of such drives can be hindered by the accumulation of resistant alleles. To limit this obstacle, we engineer a confinable population modification Home-and-Rescue (HomeR) drive in Drosophila targeting an essential gene. In our experiments, resistant alleles that disrupt the target gene function were recessive lethal, and therefore disadvantaged. We demonstrate that HomeR can achieve an increase in frequency in population cage experiments, but that fitness costs due to the Cas9 insertion limit drive efficacy.
Engineered expression of the invertebrate-specific scorpion toxin AaHIT reduces adult longevity and female fecundity in the diamondback moth Plutella xylostella
16653T. Harvey-Samuel, X. Xu, E. Lovett, T. Dafa'alla, A. Walker, V. C. Norman, R. Carter, J. Teal, L. Akilan, P. T. Leftwich, C. M. Reitmayer, H. A. Siddiqui and L. Alphey, Pest Management Science, 2021-03-04 17:21:00.
To increase the flexibility of future genetic pest management systems in the diamondback moth, we aimed to assess the use of a non-cell-autonomous, invertebrate-specific, neurotoxic effector ? the scorpion toxin AaHIT. This AaHIT effector was designed to be secreted by expressing cells, potentially leading to effects on distant cells, specifically neuromuscular junctions. We demonstrated the feasibility of using non-cell-autonomous effectors within a GPM context for the first time in Lepidoptera, one of the most economically damaging orders of insects. These findings provide a framework for extending this system to other pest Lepidoptera and to other secreted effectors.
Quantifying the risk of vector-borne disease transmission attributable to genetically modified vectors
16530G. R. Hosack, A. Ickowicz and K. R. Hayes, Royal Society Open Science, 8:201525. 2021-03-03 18:28:51.
The relative risk of disease transmission caused by the potential release of transgenic vectors, such as through sterile insect technique or gene drive systems, is assessed with comparison with wild-type vectors. The probabilistic risk framework is demonstrated with an assessment of the relative risk of lymphatic filariasis, malaria and o'nyong'nyong arbovirus transmission by mosquito vectors to human hosts given a released transgenic strain of Anopheles coluzzii carrying a dominant sterile male gene construct. Harm is quantified by a logarithmic loss function that depends on the causal risk ratio, which is a quotient of basic reproduction numbers derived from mathematical models of disease transmission. The basic reproduction numbers are predicted to depend on the number of generations in an insectary colony and the number of backcrosses between the transgenic and wild-type lineages. Analogous causal risk ratios for short-term exposure to a single cohort release are also derived. These causal risk ratios were parametrized by probabilistic elicitations, and updated with experimental data for adult vector mortality. For the wild-type, high numbers of insectary generations were predicted to reduce the number of infectious human cases compared with uncolonized wild-type. Transgenic strains were predicted to produce fewer infectious cases compared with the uncolonized wild-type.
Developing GDi-CRISPR System for Multi-copy Integration in Saccharomyces cerevisiae
16544Z.-X. Zhang, Y.-Z. Wang, Y.-S. Xu, X.-M. Sun and H. Huang, Applied Biochemistry and Biotechnology, 2021-03-03 16:12:03.
This study aims to develop a low-cost and easy-to-use multi-copy integration tool in S. cerevisiae. Firstly, twenty-one Cas proteins from different microorganisms were tested in S. cerevisiae to find the functional Cas proteins with optimal cleavage ability. Results showed that eight Cas proteins can complete gene editing. However, most of the transformants have low copy numbers, which may be caused by high cutting efficiency exceeding the repair rate. Therefore, the effect of donor translocation order was further investigated. Results showed that 4 copies were obtained by donor first translocation. Then, the gene drive delta site integration system by the CRISPR system (GDi-CRISPR) was developed by combining gene drive principle and CRISPR system. To be clear, the gRNA was put into donor fragments. Then, both of them were integrated into the genome, which can drive further cutting and repair due to increasing number of gRNA. Instead of high-throughput screening or resistance pressure, 6 copies were obtained in only 5–6 days using the GDi-CRISPR system. It is expected to further advance the development of S. cerevisiae multi-copy integration tools.
Knowledge, Attitude, and Practices Survey in Greece before the Implementation of Sterile Insect Technique against Aedes albopictus
16661A. Stefopoulou, S. L. LaDeau, N. Syrigou, G. Balatsos, V. Karras, I. Lytra, E. Boukouvala, D. P. Papachristos, P. G. Milonas, A. Kapranas, P. Vahamidis and A. Michaelakis, Insects, 12. 2021-03-02 13:52:16.
A KAP tool was used to shed light on the knowledge, practices, and attitudes of local community members in order to better prepare and motivate participation in household mosquito control and to assess current understanding of SIT. Each household also received specific information about mosquito source habitat in their own yards at the time of the initial KAP survey. These household data were complemented by standardized mosquito trapping in the municipality. Our findings indicate that citizens’ attitude toward SIT ranged from indecisive to fully supportive, while 77.5% of the respondents agreed that the SIT has many advantages over chemical control methods. Furthermore, the results demonstrate that using the door-to-door campaign as an intervention and prerelease method before SIT can suppress the initial mosquito population and potentially improve its efficacy. Lastly, we show that the presence of local municipality officials during door-to-door visits was associated with increased willingness from the residents to participate in the intervention.
Demographic and psychographic drivers of public acceptance of novel invasive pest control technologies
17086F. Eppink, P. J. Walsh and E. MacDonald, Ecology and Society, 26. 2021-03-01 15:15:26.
Invasive mammals are a primary threat to New Zealand's endemic species. In remote areas, aerial delivery of poison is the preferred method of pest management, although it faces some public backlash. Novel pest control technologies are currently being investigated as alternatives but may face similar concerns. To investigate potential social and demographic determinants of public perceptions of new methods for pest control, we conducted a national choice experiment, focused on several novel technologies: gene drives, Trojan females, and species-specific poisons. We found that preferences strongly depend on the type of technology, with Trojan female technology strictly preferred to the other two. Although several characteristics affected preferences in predictable ways education, trust in science, and liberal political leaning increased acceptance ;the same did not hold with preferences for aerial delivery. Our results are useful for targeting future engagement campaigns and leveraging existing efforts.
Meiotic drive does not cause condition-dependent reduction of the sexual ornament in stalk-eyed flies
17034S. R. Finnegan, M. Mondani, K. Fowler and A. Pomiankowski, Journal of Evolutionary Biology, 11. 2021-02-28 11:18:46.
Meiotic drive systems are associated with low-frequency chromosomal inversions. These are expected to accumulate deleterious mutations due to reduced recombination and low effective population size. We test this prediction using the 'sex-ratio' (SR) meiotic drive system of the Malaysian stalk-eyed fly Teleopsis dalmanni. SR is associated with a large inversion (or inversions) on the X chromosome. In particular, we study eyespan in males carrying the SR chromosome, as this trait is a highly exaggerated, sexually dimorphic trait, known to have heightened condition-dependent expression. Larvae were raised in low and high larval food stress environments. SR males showed reduced eyespan under the low and high stress treatments, but there was no evidence of a condition-dependent decrease in eyespan under high stress. Similar but more complex patterns were observed for female eyespan, with evidence of additivity under low stress and heterosis under high stress. These results do not support the hypothesis that reduced sexual ornament size in meiotic drive males is due to a condition-dependent response to the putative increase in mutation load. Instead, reduced eyespan likely reflects compensatory resource allocation to different traits in response to drive-mediated destruction of sperm.
Designing gene drives to limit spillover to non-target populations
16516G. Greenbaum, M. W. Feldman, N. A. Rosenberg and J. Kim, PLOS Genetics, 17:e1009278. 2021-02-25 15:02:27.
We develop mathematical models of gene-drive dynamics that incorporate migration between a target and non-target populations to investigate the possibility of effectively applying a gene drive in the target population while limiting its spillovers to the non-target population (‘differential targeting’). We observe that the feasibility of differential targeting depends on the gene-drive design specification, as well as on the migration rates between the populations. Even when differential targeting is possible, as migration increases, the possibility for differential targeting disappears. We find that differential targeting can be effective for low migration rates, and that it is sensitive to the design of the gene drive under high migration rates. We suggest that differential targeting could be used, in combination with other mitigation measures, as an additional safeguard to limit gene drive spillovers.
Sterile Insect Technique: Lessons From the Past
18706M. Q. Benedict, Journal of Medical Entomology, 58:1974-1979. 2021-02-25 13:35:08.
When E.F. Knipling conceived of the release of sexually sterile insects to suppress wild populations, he laid down several fundamental qualities that characterized suitable target species—some of which mosquitoes generally violate—including high reproductive rates and large population numbers. Regardless of this, their global importance in public health has led numerous research teams to attempt to use the mosquito sterile insect technique against several species. Because of the degree of financial commitment required for suppression programs, most releases have consisted of preliminary investigations of male performance, population characteristics, and production methods. Those that have accomplished suppression provide important insights regarding the challenges of production, dispersal, and immigration. Insights gained from these studies remain relevant today, regardless of the genetic control technology being applied. In this article, I highlight studies that were notable for the insights that were gained, the intrinsic difficulties that mosquitoes present, and synthesize these into recommendations for successful applications of the sterile insect technique and newer technologies to mosquitoes.
Sterile Insect Technique (SIT) against Aedes Species Mosquitoes: A Roadmap and Good Practice Framework for Designing, Implementing and Evaluating Pilot Field Trials
16659C. F. Oliva, M. Q. Benedict, C. M. Collins, T. Baldet, R. Bellini, H. Bossin, J. Bouyer, V. Corbel, L. Facchinelli, F. Fouque, M. Geier, A. Michaelakis, D. Roiz, F. Simard, C. Tur and L.-C. Gouagna, Insects, 12. 2021-02-24 13:44:35.
We offer here a pragmatic and accessible ‘roadmap’ for the pre-pilot and pilot phases to guide any interested party. This will support stakeholders, non-specialist scientists, implementers, and decision-makers. Applying these concepts will ensure, given adequate resources, a sound basis for local field trialing and for developing experience with the technique in readiness for potential operational deployment. This synthesis is based on the available literature, in addition to the experience and current knowledge of the expert contributing authors in this field. We describe a typical path to successful pilot testing, with the four concurrent development streams of Laboratory, Field, Stakeholder Relations, and the Business and Compliance Case. We provide a graphic framework with criteria that must be met in order to proceed.
Population genomics of invasive rodents on islands: Genetic consequences of colonization and prospects for localized synthetic gene drive
16657K. P. Oh, A. B. Shiels, L. Shiels, D. V. Blondel, K. J. Campbell, J. R. Saah, A. L. Lloyd, P. Q. Thomas, F. Gould, Z. Abdo, J. R. Godwin and A. J. Piaggio, Evolutionary Applications, 2021-02-22 17:41:41.
Here we used pooled whole-genome sequencing of invasive mouse (Mus musculus) populations on four islands along with paired putative source populations to test genetic predictions of island colonization and characterize locally fixed Cas9 genomic targets. Patterns of variation across the genome reflected marked reductions in allelic diversity in island populations and moderate to high degrees of differentiation from nearby source populations despite relatively recent colonization. Locally fixed Cas9 sites in female fertility genes were observed in all island populations, including a small number with multiplexing potential. In practice, rigorous sampling of presumptive LFA will be essential to fully assess risk of resistance alleles. These results should serve to guide development of improved, spatially limited gene drive design in future applications.
Modeling impact and cost-effectiveness of gene drives for malaria elimination in the Democratic Republic of the Congo
16477N. Metchanun, C. Borgemeister, G. Amzati, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin, medRxiv, 2020.06.29.20142760. 2021-02-22 13:51:04.
Using a spatially explicit, agent-based model of malaria transmission in eight representative provinces of the Democratic Republic of the Congo, we predict the impact and cost-effectiveness of integrating driving-Y gene drive mosquitoes in malaria elimination strategies that include existing interventions such as insecticide-treated nets and case management of symptomatic malaria. Gene drive mosquitoes could eliminate malaria and were the most cost-effective intervention overall if the drive component was highly effective with at least 95% X-shredding and associated cost of deployment below 7.17 $int per person per year. Suppression gene drive could be a cost-effective supplemental intervention for malaria elimination, but tight constraints on drive effectiveness and cost ceilings may limit its feasibility.
Holocentric Chromosomes Probably Do Not Prevent Centromere Drive in Cyperaceae
16676M. Kratka, J. Smerda, K. Lojdova, P. Bures and F. Zedek, Frontiers in Plant Science, 12:9. 2021-02-19 14:30:42.
In response to these selfish centromeres, the histone protein CenH3, which recruits kinetochore components, adaptively evolves to restore chromosomal parity and counter the detrimental effects of centromere drive. Holocentric chromosomes, whose kinetochores are assembled along entire chromosomes, have been hypothesized to prevent expanded centromeres from acquiring a selective advantage and initiating centromere drive. In such a case, CenH3 would be subjected to less frequent or no adaptive evolution. Using codon substitution models, we analyzed 36 CenH3 sequences from 35 species of the holocentric family Cyperaceae. We found 10 positively selected codons in the CenH3 gene [six codons in the N-terminus and four in the histone fold domain (HFD)] and six branches of its phylogeny along which the positive selection occurred. One of the positively selected codons was found in the centromere targeting domain (CATD) that directly interacts with DNA and its mutations may be important in centromere drive suppression. The frequency of these positive selection events was comparable to the frequency of positive selection in monocentric clades with asymmetric female meiosis. Taken together, these results suggest that preventing centromere drive is not the primary adaptive role of holocentric chromosomes, and their ability to suppress it likely depends on their kinetochore structure in meiosis.
Split versions of Cleave and Rescue selfish genetic elements for measured self limiting gene drive
16426G. Oberhofer, T. Ivy and B. A. Hay, PLoS genetics, 17:e1009385. 2021-02-18 20:00:28.
Self-sustaining Cleave and Rescue (ClvR) elements include a DNA sequence-modifying enzyme such as Cas9/gRNAs that disrupts endogenous versions of an essential gene, a tightly linked recoded version of the essential gene resistant to cleavage (the Rescue), and a Cargo. ClvR spreads by creating loss-of-function (LOF) conditions in which those without ClvR die because they lack functional copies of the essential gene. We use modeling to show that when the Rescue-Cargo and one or both components required for LOF allele creation (Cas9 and gRNA) reside at different locations (split ClvR), drive of Rescue-Cargo is self-limiting due to a progressive decrease in Cas9 frequency, and thus opportunities for creation of LOF alleles, as spread occurs. Importantly, drive strength and duration can be extended in a measured manner-which is still self-limiting-by moving the two components close enough to each other that they experience some degree of linkage. With linkage, Cas9 transiently experiences drive by hitchhiking with Rescue-Cargo until linkage disequilibrium between the two disappears, a function of recombination frequency and number of generations, creating a novel point of control. We implement split ClvR in Drosophila, with key elements on different chromosomes. Cargo/Rescue/gRNAs spreads to high frequency in a Cas9-dependent manner, while the frequency of Cas9 decreases.
Emergent challenges for CRISPR: biosafety, biosecurity, patenting, and regulatory issues
19398Braddick, D. , and Ramarohetra, R. F., Genome Engineering Via Crispr-Cas9 System, 2021-02-18 17:46:33.
The recent advancements of CRISPR-Cas technologies have transformed this simple and efficient gene editing technique into an extraordinarily powerful tool. The most anticipated applications could create novel therapeutics against mankind's most serious afflictions and help eradicate vector-based diseases. However, with these desired benefits come new ethical questions and potential threats. CRISPR technologies are not yet fully developed toward delivering all of their promises, and suffer from biosafety problems in human products and biosecurity threats arising from its potential dual use and errant gene drives. Furthermore, the future innovations of CRISPR technologies may encounter non-scientific challenges in patentability and unclear legal regulations at the national and international levels. This chapter will discuss these issues, and where possible, will highlight the currently proposed solutions that could mitigate the threats, and could address the problems that hold back CRISPR's full potential.
Scientifically framed gene drive communication perceived as credible but riskier
16406E. A. MacDonald, E. D. Edwards, J. Balanovic and F. Medvecky, People and Nature, 2021-02-17 18:23:29.
Framing is a communication technique in which certain beliefs or values are emphasized that resonate with the target audience. Framing may increase how much people objectively think about new information and update their opinions; framing may mitigate emo
ReMOT Control Delivery of CRISPR-Cas9 Ribonucleoprotein Complex to Induce Germline Mutagenesis in the Disease Vector Mosquitoes Culex pipiens pallens (Diptera: Culicidae)
17482X. X. Li, Y. Xu, H. B. Zhang, H. T. Yin, D. Zhou, Y. Sun, L. Ma, B. Shen and C. L. Zhu, Journal of Medical Entomology, 58. 2021-02-16 14:57:35.
The wide distribution of Culex (Cx.) pipiens complex mosquitoes makes it difficult to prevent the transmission of mosquito-borne diseases in humans. Gene editing using CRISPR/Cas9 is an effective technique with the potential to solve the growing problem of mosquito-borne diseases. This study uses the ReMOT Control technique in Culex pipiens pallens (L.) to produce genetically modified mosquitoes. A microinjection system was established by injecting 60 adult female mosquitoes-14 mu l injection mixture was required, and no precipitation occurred with <= 1 mu l of endosomal release reagents (chloroquine or saponin). The efficiency of delivery of the P2C-enhanced green fluorescent protein-Cas9 (P2C-EGFP-Cas9) ribonucleoprotein complex into the ovary was 100% when injected at 24 h post-bloodmeal (the peak of vitellogenesis). Using this method for KMO knockout, we found that gene editing in the ovary could also occur when P2C-Cas9 RNP complex was injected into the hemolymph of adult Cx. pipiens pallens by ReMOT Control. In the chloroquine group, of the 2,251 G(0) progeny screened, 9 individuals showed with white and mosaic eye phenotypes. In the saponin group, of the 2,462 G(0) progeny screened, 8 mutant individuals were observed. Sequencing results showed 13 bp deletions, further confirming the fact that gene editing occurred. In conclusion, the successful application of ReMOT Control in Cx. pipiens pallens not only provides the basic parameters (injection parameters and injection time) for this method but also facilitates the study of mosquito biology and control.
Operational Parameters for the Aerial Release of Sterile Codling Moths Using an Uncrewed Aircraft System
17762E. D. Esch, R. M. Horner, D. C. Krompetz, N. Moses-Gonzales, M. R. Tesche and D. M. Suckling, Insects, 12:2/13/2021. 2021-02-13 14:52:13.
The codling moth is a serious pest of apples in most regions of the world where this fruit is produced. The sterile insect technique is one strategy used to control this pest and is employed as part of an area-wide integrated pest management program for the codling moth in British Columbia, Canada. Modified fixed wing aircraft are the most common method for the release of sterile insects in large area-wide pest management programs. However, aerial release with a full-size aircraft can be prohibitively expensive. We evaluated the use of small, uncrewed aircraft systems (UASs) for the release of sterile codling moths. Sterile codling moths released from greater altitudes were more broadly distributed and drifted more in strong winds, compared to those released from lower altitudes. Most of the released insects were recaptured in a 50 m wide swath under the release route. Recapture rates for aerially released insects were 40–70% higher compared to those released from the ground. UASs provide a promising alternative to ground release and conventional aircraft for the release of sterile codling moths.
Optimized CRISPR tools and site-directed transgenesis in Culex quinquefasciatus mosquitoes for gene drive development
16372X. Feng, V. Lopez Del Amo, E. Mameli, M. Lee, A. L. Bishop, N. Perrimon and V. M. Gantz, bioRxiv, 2021.02.10.430702. 2021-02-11 20:33:00.
Here, we developed a Culex-specific Cas9/gRNA expression toolkit and used site-directed homology-based transgenesis to generate and validate a Culex quinquefasciatus Cas9-expressing line. We showed that gRNA scaffold variants improve transgenesis efficiency in both Culex and Drosophila and boost gene-drive performance in the fruit fly. These findings support future technology development to control Culex mosquitoes and provide valuable insight for improving these tools in other species.
Hidden genomic features of an invasive malaria vector, Anopheles stephensi, revealed by a chromosome-level genome assembly
16376M. Chakraborty, A. Ramaiah, A. Adolfi, P. Halas, B. Kaduskar, L. T. Ngo, S. Jayaprasad, K. Paul, S. Whadgar, S. Srinivasan, S. Subramani, E. Bier, A. A. James and J. J. Emerson, BMC Biology, 19:28. 2021-02-10 20:40:13.
The mosquito Anopheles stephensi is a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis of vectorial capacity and engineering genetic interventions are both impeded by limitations of a vector’s genome assembly. The existing assemblies of An. stephensi are draft-quality and contain thousands of sequence gaps, potentially missing genetic elements important for its biology and evolution.
A Code of Ethics for Gene Drive Research
16379G. J. Annas, C. L. Beisel, K. Clement, A. Crisanti, S. Francis, M. Galardini, R. Galizi, J. Grünewald, G. Immobile, A. S. Khalil, R. Müller, V. Pattanayak, K. Petri, L. Paul, L. Pinello, A. Simoni, C. Taxiarchi and J. K. Joung, The CRISPR Journal, 4:19:1-8. 2021-02-10 14:57:13.
A code of ethics can be a useful tool for all parties involved in the development and regulation of gene drives and can be used to help ensure that a balanced analysis of risks, benefits, and values is taken into consideration for the interest of society and humanity. We have developed a code of ethics for gene drive research with the hope that this code will encourage the development of an international framework that includes ethical guidance of gene drive research and is incorporated into scientific practice by gaining broad agreement and adherence.
In Our Image: The Ethics of CRISPR Genome Editing
16272J. C. Eissenberg, Biomolecular Concepts, 12:1-7. 2021-02-06 16:55:38.
Here, I discuss the ethics surrounding the transformative CRISPR/Cas9mediated genome editing technology in the contexts of human genome editing to eradicate genetic disease and of gene drive technology to eradicate animal vectors of human disease.
How to engage communities on a large scale? Lessons from World Mosquito Program in Rio de Janeiro, Brazil [version 2; peer review: 1 approved, 2 approved with reservations]
16361G. B. Costa, R. Smithyman, S. L. O'Neill and L. A. Moreira, Gates Open Research, 2021-02-04 19:26:09.
Here we discuss and analyse the framework for community engagement implemented by the WMP in Brazil, during the large-scale deployment of the method in the municipalities of Niterói and Rio de Janeiro, Brazil. Our experience indicates that the community engagement work for arboviruses control should be understood as an opportunity for local development. It is necessary, based on an integrated analysis of the territory, to understand that the actions for arboviruses control could be a catalyst for the necessary socioenvironmental, cultural and public health changes. Furthermore, it is essential to understand that community engagement goes beyond informing or asking for population consent, but it constitutes a possibility for dialogue and exchange between the various stakeholders present in the territories, to build on cooperation for mosquito-borne disease control.
Reply to: Issues with combining incompatible and sterile insect techniques
16265Y. Li, L. A. Baton, D. Zhang, J. Bouyer, A. G. Parker, A. A. Hoffmann, L. C. Ng, C. H. Tan and Z. Xi, Nature, 590:E3-E5. 2021-02-04 16:31:29.
When the aim is elimination of the target population, Uni-CI and Bi-CI do not have appreciably different risks of population replacement. The small-scale field trial8 cited by Moretti and Calvitti in their Comment1 does not provide evidence that Bi-CI protects against population replacement during IIT, as the occurrence of the released Wolbachia strain in the field was not determined and the level of population suppression was insufficient to facilitate surpassing of the invasion threshold.
The complete mitogenome sequence of the agricultural pest, clover root weevil: the key to its own demise?
18799R. A. Al-Jiab, J. Gillum, A. Alexander, D. M. Tompkins, C. B. Phillips, P. K. Dearden and N. J. Gemmell, Mitochondrial DNA Part B, 4:878-879. 2021-02-03 18:44:34.
AbstractWe report the complete mitogenome of Sitona obsoletus, an agricultural pest in New Zealand and some European countries. Like other Sitona mitogenomes, the 6 tRNA gene box is ordered RNSAEF, supporting the hypothesis that this signature is common to, and potentially diagnostic, of this genus. The Trojan Female Technique (TFT) is a genetic pest control strategy that exploits mitochondrial DNA alleles that affect male, but not female fertility and fitness. The complete mitogenome is an essential first step in exploring the utility of TFT for the control of S. obsoletus.
Issues with combining incompatible and sterile insect techniques
16261R. Moretti and M. Calvitti, Nature, 590:E1-E2. 2021-02-03 16:00:45.
In a recent paper, Zheng at al.1 performed field experiments that tested a strategy of mosquito suppression based on the release of functionally sterile males produced by the combination of reproductive unidirectional cytoplasmic incompatibility (which is induced by the bacterium Wolbachia) and a sterilization treatment caused by X-rays. In our opinion, the authors do not present an exhaustive description of the current status in this field, and their results highlight several practical weaknesses in this strategy.
Improving the Phenotypic Properties of the Ceratitis capitata (Diptera: Tephritidae) Temperature-Sensitive Lethal Genetic Sexing Strain in Support of Sterile Insect Technique Applications
16226M. F. Porras, J. S. Meza, E. G. Rajotte, K. Bourtzis and C. Caceres, Journal of Economic Entomology, 113:2688-2694. 2021-01-31 16:33:01.
We present the first evidence that this slower development is due to a different gene, here namely slow development (sd), which is closely linked to the tsl gene. Taking advantage of recombination phenomena between the two loci, we report the isolation of a novel temperature sensitivity lethal strain using the wp mutation as a morphological marker, which showed faster development (wp tsl FD) during the larval stage and increased in its temperature sensitivity compared with the normal tsl strain. Moreover, the introgression of this novel wp tsl FD combined trait into the Vienna 8(D53-) GSS, resulted in a novel Vienna 8(D53-) FD GSS, where females showed differences in the thermal sensibility, larval development speed, and productivity profiles. The modification of these traits and their impact on the mass rearing of the GSS for sterile insect technique applications are discussed.
Regulating the expression of gene drives is key to increasing their invasive potential and the mitigation of resistance
16290A. Hammond, X. Karlsson, I. Morianou, K. Kyrou, A. Beaghton, M. Gribble, N. Kranjc, R. Galizi, A. Burt, A. Crisanti and T. Nolan, PLOS Genetics, 17:e1009321. 2021-01-29 21:53:25.
Here we show that restricting the cutting activity of the gene drive to the germline tissue is crucial to maintaining its potency and we illustrate how failure to restrict this activity can lead to the generation of mutations that can make mosquitoes resistant to the gene drive.
Sexual Competitiveness and Induced Egg Sterility by Aedes aegypti and Aedes albopictus Gamma-Irradiated Males: A Laboratory and Field Study in Mexico
17760J. G. Bond, S. Aguirre-Ibáñez, A. R. Osorio, C. F. Marina, Y. Gómez-Simuta, R. Tamayo-Escobar, A. Dor, P. Liedo, D. O. Carvalho and T. Williams, Insects, 12. 2021-01-29 14:44:07.
The sterile insect technique may prove useful for the suppression of mosquito vectors of medical importance in regions where arboviruses pose a serious public health threat. In the present study, we examined the effects of sterilizing irradiation doses across different ratios of fertile:irradiated males on the mating competitiveness of Ae. aegypti and Ae. albopictus under laboratory and field-cage conditions. For both species, the percentage of females inseminated and the number of eggs laid over two gonotrophic cycles varied significantly in mating treatments involving 1:1, 1:5, and 1:10 fertile:irradiated males compared to controls of entirely fertile or entirely irradiated males but was not generally affected by the irradiation dose. Egg hatching was negatively affected in females exposed to increasing proportions of irradiated males in both laboratory and field cages. Male competitiveness (Fried’s index) values varied from 0.19 to 0.58 in the laboratory and were between 0.09 and 1.0 in field cages, depending on th species. Competitiveness values were negatively affected by th eirradiation dose in both species under field-cage conditions, whereas in the laboratory, Ae. albopictus was sensitive to the dose but Ae. aegypti was not. In general, male competitiveness was similar across all mating regimes. Most importantly, induced egg sterility was positively correlated with the proportion of irradiated males present in the mating treatments, reaching a maximum of 88% under field-cage conditions for both Ae. aegypti and Ae. albopictus males treated with 50 and 40 Gy irradiation, respectively. These results indicate that sterile males produced at our facility are suitable and competitive enough for field pilot SIT projects and provide guidance to decide the optimal sterile:fertile ratios.
GENE DRIVE ACCEPTANCE SURVEY
16233YouGov, Pollinis, 2021-01-27 16:47:37.
This representative survey was conducted by the international market research institute YouGov and polled 8.826 citizens from 8 EU countries in December 2020. It was commissioned by WeMove Europe, Save Our Seeds (Germany), Skiftet (Sweden), France Nature Environnement (FNE) (France), POLLINIS (France), OGM Dangers (France), Bund für Umwelt und Naturschutz (BUND) (Germany), Deutscher Naturschutzring (DNR) (Germany), Umweltinstitut München (Germany), Za Zemiata (Bulgaria). Deviations from 100% are due to rounding.
Demographic feedbacks can hamper the spatial spread of a gene drive
16203L. Girardin and F. Débarre, arXiv, 2021-01-27 15:32:53.
Our results indicate that taking into account the interplay between population dynamics and population genetics might actually be crucial, as it can effectively reverse the direction of the invasion and lead to failure. Our findings can be extended to other bistable systems, such as the spread of cytoplasmic incompatibilities caused by Wolbachia.
Playing God and tampering with nature: popular labels for real concerns in synthetic biology
16201L. Carter, A. Mankad, E. V. Hobman and N. B. Porter, Transgenic Research, 2021-01-27 15:26:41.
We present the findings from a large Australian study (N = 4593) which suggests ‘playing God’ objections and their variants can be multilayered and, at times, accompanied by meaningful information about risk perceptions. We use qualitative analysis of ope
Anopheles gambiae Genome Conservation as a Resource for Rational Gene Drive Target Site Selection
16102N. Kranjc, A. Crisanti, T. Nolan and F. Bernardini, Insects, 12. 2021-01-23 14:46:16.
In this study we describe a bioinformatic pipeline that allows the analysis of whole genome data for the identification of highly conserved regions that can point at potential functional or structural constraints. The analysis was conducted across the genomes of 22 insect species separated by more than hundred million years of evolution and includes the observed genomic variation within field caught samples of Anopheles gambiae and Anopheles coluzzii, the two most dominant malaria vectors. This study offers insight into the level of conservation at a genome-wide scale as well as at per base-pair resolution.
Drivers of mosquito mating
16110N. C. Manoukis, Science, 371:340. 2021-01-22 15:54:49.
Gene drive systems are based on the release of organisms whose genomes have been modified or engineered to spread a desired allele or trait (such as resistance to the parasites that cause malaria) through a population. Success will depend on the release of genetically modified males that will be able to mate with wild females. Beyond gene drive strategies, in mosquitoes it is understood that only males can be released as part of any genetic pest control (GPC) program (7); females feed on blood to lay eggs, and releasing insects that will feed on humans is widely unacceptable.
Clock genes and environmental cues coordinate Anopheles pheromone synthesis, swarming, and mating
16108G. Wang, J. Vega-Rodríguez, A. Diabate, J. Liu, C. Cui, C. Nignan, L. Dong, F. Li, C. O. Ouedrago, A. M. Bandaogo, P. S. Sawadogo, H. Maiga, T. L. Alves e Silva, T. V. Pascini, S. Wang and M. Jacobs-Lorena, Science, 371:411. 2021-01-22 15:35:30.
Knockdown of per and tim expression affects Anopheles gambiae s.s. and Anopheles stephensi male mating in the laboratory, and it reduces male An. coluzzii swarming and mating under semifield conditions. Light and temperature affect mosquito mating, possibly by modulating per and/or tim expression. Moreover, the desaturase gene desat1 is up-regulated and rhythmically expressed in the heads of swarming males and regulates the production of cuticular hydrocarbons, including heptacosane, which stimulates mating activity.
The Promises and Realities of Integration in Synthetic Biology: A View From Social Science
16287L. Carter and A. Mankad, Frontiers in Bioengineering and Biotechnology, 8. 2021-01-21 17:25:32.
We take stock of thepromises and realities of science integration by sharing our experiences of embarking onthis very challenge in Australia. We conclude by offering suggestions for bringing aboutthe enabling conditions for improved integration across the natural and social sciences.Four key actions are articulated to help pivot synthetic biology toward a more integratedscientific endeavor: (a) formalizing inclusivity from inception to project conclusion; (b)valuing differing philosophical positions as a strength rather than a barrier; (c) acceptingthat integration takes persistence and communication but is immensely rewarding; and(d) promoting meaningful interactions, such as pursuing joint opportunities, co-designingand co-publishing research. We argue that these actions arekey enablers for realizingscience integration in synthetic biology.
White pupae phenotype of tephritids is caused by parallel mutations of a MFS transporter
16691C. M. Ward, R. A. Aumann, M. A. Whitehead, K. Nikolouli, G. Leveque, G. Gouvi, E. Fung, S. J. Reiling, H. Djambazian, M. A. Hughes, S. Whiteford, C. Caceres-Barrios, T. N. M. Nguyen, A. Choo, P. Crisp, S. B. Sim, S. M. Geib, F. Marec, I. Hacker, J. Ragous, Nature Communications, 12. 2021-01-21 15:50:54.
Here, we use classical and modern genetic approaches to identify and functionally characterize causal wp(-) mutations in these distantly related fruit fly species. We find that the wp phenotype is produced by parallel mutations in a single, conserved gene. CRISPR/Cas9-mediated knockout of the wp gene leads to the rapid generation of white pupae strains in C. capitata and B. tryoni. The conserved phenotype and independent nature of wp(-) mutations suggest this technique can provide a generic approach to produce sexing strains in other major medical and agricultural insect pests. The white pupae (wp) phenotype has been used for decades to selectively remove females of tephritid species in genetic sexing, but the determining gene is unknown. Here, the authors show that wp phenotype is produced by parallel mutations in a Major Facilitator Superfamily domain containing gene across multiple species.
Co‐developing a common glossary with stakeholders for engagement on new genetic approaches for malaria control in a local African setting
16104E. Chemonges Wanyama, B. Dicko, L. Pare Toe, M. B. Coulibaly, N. Barry, K. Bayala Traore, A. Diabate, M. Drabo, J. K. Kayondo, S. Kekele, S. Kodio, A. D. Ky, R. R. Linga, E. Magala, W. I. Meda, S. Mukwaya, A. Namukwaya, B. Robinson, H. Samoura, K. Sanogo, Malaria Journal, 20:53. 2021-01-21 14:51:47.
Scientific terminologies are mainly lacking in local languages, yet when research activities involve international partnership, the question of technical jargon and its translation is crucial for effective and meaningful communication with stakeholders. Target Malaria, a not-for-profit research consortium developing innovative genetic approaches to malaria vector control, carried out a linguistic exercise in Mali, Burkina Faso and Uganda to establish the appropriate translation of its key terminology to local languages of sites where the teams operate.
Combining refuges with transgenic insect releases for the management of an insect pest with non-recessive resistance to Bt crops in agricultural landscapes
17006T. R. Brewer and M. B. Bonsall, Journal of Theoretical Biology, 509:11. 2021-01-21 12:35:03.
Reinforcing the high-dose/refuge strategy with releases of transgenic insects has been suggested as a method for simultaneously managing agricultural pest populations and resistance to transgenic crops. Theoretical and empirical studies have shown that these approaches can work when deployed against closed populations and the assumptions of the HDR strategy are met. However, field-evolved resistance is often linked to non-recessive resistance or refuge non-compliance, and pest management regimes are likely to take place at the landscape-level. It is therefore important to understand how effective such strategies are when resistance is non-recessive, and how they could be employed in agricultural landscapes. We developed a spatially-explicit model to investigate the efficacy of strategies combining refuges with transgenic insect releases to manage a pest with non-recessive resistance in agricultural landscapes. We compared two release strategies, area-wide releases and localised releases targeted at population hotspots, and analysed the effects of refuge and release parameters on population and resistance dynamics. Area-wide releases reliably achieved landscape-level pest eradication. Localised releases also eradicated the pest when low release thresholds were combined with high release ratios, and maintained the pest at low densities when insufficient to achieve extinction. Reinforcing refuges with localised releases also greatly enhanced the probability of resistance extinction. However, when resistance remained in the population, localised releases prevented resistance from reaching fixation rather than greatly delaying or reversing resistance evolution. Our work indicates that combining refuges with simple release policies is effective for landscape-level pest suppression when the HDR assumptions are violated, but more nuanced release strategies may be required to enhance the benefits to resistance management. (C) 2020 Elsevier Ltd. All rights reserved.
Manipulation of Gut Symbionts for Improving the Sterile Insect Technique: Quality Parameters of Bactrocera dorsalis (Diptera: Tephritidae) Genetic Sexing Strain Males After Feeding on Bacteria-Enriched Diets
17222Q. Zhang, P. Cai, B. Wang, X. Liu, J. Lin, R. Hua, H. Zhang, C. Yi, X. Song, Q. Ji, J. Yang and S. Chen, Journal of Economic Entomology, 114:560-570. 2021-01-18 16:16:41.
One environmentally friendly method used to manage Bactrocera dorsalis (Hendel), a key agricultural pest of substantial economic importance, is the sterile insect technique (SIT). Nevertheless, several deficiencies related to this strategy impair the success of the SIT, including the inferior performance of released sterile males compared with wild males, which could be partly solved by the utilization of gut symbionts as probiotic dietary components. In this study, a culture-dependent method was used to isolate and characterize gut-associated bacterial species in adult B. dorsalis genetic sexing strain (GSS) males. In addition, three bacterial isolates from the Enterobacteriaceae family, namely, Enterobacter sp., Morganella morganii, and Moellerella wisconsensis, were used as supplements in larval and adult diets to assess their effects on the life-history traits of irradiated males. Consistent with many previous studies, Enterobacter spp. was shown to be beneficial, with some quality control indices, such as adult size, pupal weight, survival rate under stress and nutritionally rich conditions, and mating competitiveness, being significantly increased, while slight nonsignificant increases in emergence rate and flight ability were observed. Conversely, the M. morganii and M. wisconsensis strains both had negative effects on irradiated male fitness and mating competitiveness. Our results, in combination with those of earlier studies, can contribute to improving the effectiveness of SIT application by enhancing the different aspects of augmentative rearing and biological traits of pests under laboratory rearing conditions.
Widespread haploid-biased gene expression enables sperm-level natural selection
16009K. Bhutani, K. Stansifer, S. Ticau, L. Bojic, A.-C. Villani, J. Slisz, C. M. Cremers, C. Roy, J. Donovan, B. Fiske and R. C. Friedman, Science, eabb1723. 2021-01-14 14:15:08.
Here, we show that a large class of mammalian genes are not completely shared across these bridges. We term these genes “genoinformative markers” (GIMs) and show that a subset can act as selfish genetic elements that spread alleles unevenly through murine, bovine, and human populations. We identify evolutionary pressure to avoid conflict between sperm and somatic function as GIMs are enriched for testis-specific gene expression, paralogs, and isoforms.
Selfing is the safest sex for Caenorhabditis tropicalis
15953L. M. Noble, J. Yuen, L. Stevens, N. D. Moya, R. Persaud, M. Moscatelli, J. L. Jackson, G. Zhang, R. Chitrakar, L. R. Baugh, C. Braendle, E. C. Andersen, H. S. Seidel and M. V. Rockman, eLife, 10:e62587. 2021-01-11 16:59:39.
We generated a chromosomal-scale genome for C. tropicalis and surveyed global diversity. Population structure is very strong, and islands of extreme divergence punctuate a genomic background that is highly homogeneous around the globe. Outbreeding depression in the laboratory is caused largely by multiple Medea-like elements, genetically consistent with maternal toxin/zygotic antidote systems. Loci with Medea activity harbor novel and duplicated genes, and their activity is modified by mito-nuclear background. Segregating Medea elements dramatically reduce fitness, and simulations show that selfing limits their spread. Frequent selfing in C. tropicalis may therefore be a strategy to avoid Medea-mediated outbreeding depression.
Population Dynamics of Aedes aegypti and Aedes albopictus in Two Rural Villages in Southern Mexico: Baseline Data for an Evaluation of the Sterile Insect Technique
17758C. F. Marina, J. G. Bond, K. Hernández-Arriaga, J. Valle, A. Ulloa, I. Fernández-Salas, D. O. Carvalho, K. Bourtzis, A. Dor, T. Williams and P. Liedo, Insects, 12. 2021-01-11 14:36:35.
Indoor and outdoor ovitraps were placed in 15 randomly selected houses in two rural villages in Chiapas, southern Mexico. In addition, ovitraps were placed in five transects surrounding each village, with three traps per transect, one at the edge, one at 50 m, and another at 100 m from the edge of the village. All traps were inspected weekly. A transect with eight traps along a road between the two villages was also included. Population fluctuations of Aedes aegypti and Ae. albopictus were examined during 2016–2018 by counting egg numbers. A higher number of Aedes spp. eggs was recorded at Hidalgo village with 257,712 eggs (60.9%), of which 58.1% were present in outdoor ovitraps and 41.9% in indoor ovitraps, compared with 165,623 eggs (39.1%) collected in the village of Río Florido, 49.0% in outdoor and 51.0% in indoor ovitraps. A total of 84,047 eggs was collected from ovitraps placed along transects around Río Florido, compared to 67,542 eggs recorded from transects around Hidalgo. Fluctuations in egg counts were associated with annual variation in precipitation, with 2.3 to 3.2-fold more eggs collected from ovitraps placed in houses and 4.8 to 5.1-fold more eggs in ovitraps from the surrounding transects during the rainy season than in the dry season, respectively. Aedes aegypti was the dominant species during the dry season and at the start of the rainy season in both villages. Aedes albopictus populations were lower for most of the dry season, but increased during the rainy season and predominated at the end of the rainy season in both villages. Aedes albopictus was also the dominant species in the zones surrounding both villages. The numbers of eggs collected from intradomiciliary ovitraps were strongly correlated with the numbers of eggs in peridomiciliary ovitraps in both Río Florido (R2adj = 0.92) and Hidalgo (R2adj = 0.94), suggesting that peridomiciliary sampling could provide an accurate estimate of intradomiciliary oviposition by Aedes spp. in future studies in these villages. We conclude that the feasibility of sterile insect technique (SIT)-based program of vector control could be evaluated in the isolated Ae. aegypti populations in the rural villages of our baseline study.
Double drives and private alleles for localised population genetic control
15945K. Willis and A. Burt, bioRxiv, 2021.01.08.425856. 2021-01-09 16:30:16.
In this paper we propose and model a series of low threshold double drive designs for population suppression, each consisting of two constructs, one imposing a reproductive load on the population and the other inserted into a differentiated locus and controlling the drive of the first. Simple deterministic, discrete-generation computer simulations are used to assess the alternative designs. We find that the simplest double drive designs are significantly more robust to pre-existing cleavage resistance at the differentiated locus than single drive designs, and that more complex designs incorporating sex ratio distortion can be more efficient still, even allowing for successful control when the differentiated locus is neutral and there is up to 50% pre-existing resistance in the target population. Similar designs can also be used for population replacement, with similar benefits. A population genomic analysis of PAM sites in island and mainland populations of the malaria mosquito Anopheles gambiae indicates that the differentiation needed for our methods to work can exist in nature. Double drives should be considered when efficient but localised population genetic control is needed and there is some genetic differentiation between target and non-target populations.
Targeting evolutionary conserved sequences circumvents the evolution of resistance in a viral gene drive against human cytomegalovirus
15943M. Walter, R. Perrone and E. Verdin, bioRxiv, 2021.01.08.425902. 2021-01-08 16:26:29.
Here, we analyze in cell culture experiments the evolution of resistance in a gene drive against human cytomegalovirus. We report that after an initial invasion of the wildtype population, a drive-resistant population is positively selected over time and outcompetes gene drive viruses. However, we show that targeting evolutionary conserved regions ensures that drive-resistant viruses have a replication defect, leading to a long-term reduction of viral levels. This marks an important step toward developing effective gene drives in viruses, especially for therapeutic applications.
Suppression gene drive in continuous space can result in unstable persistence of both drive and wild-type alleles
15938J. Champer, I. K. Kim, S. E. Champer, A. G. Clark and P. W. Messer, Mol Ecol, 2021-01-07 19:32:54.
Using spatially explicit simulations, we show that the release of a suppression drive can result in what we term "chasing" dynamics, in which wild-type individuals recolonize areas where the drive locally eliminated the population. Despite the drive subsequently reconquering these areas, complete population suppression often fails to occur or is substantially delayed. This increases the likelihood that the drive is lost or that resistance evolves. We analyze how chasing dynamics are influenced by the type of drive, its efficiency, fitness costs, and ecological factors such as the maximal growth rate of the population and levels of dispersal and inbreeding. We find that chasing is more common for lower efficiency drives when dispersal is low and that some drive mechanisms are substantially more prone to chasing behavior than others. Our results demonstrate that the population dynamics of suppression gene drives are determined by a complex interplay of genetic and ecological factors, highlighting the need for realistic spatial modeling to predict the outcome of drive releases in natural populations.
Demystifying the Risk Assessment Process for Laboratory-Based Experiments Utilizing Invasive Genetic Elements: It Is More Than Gene Drive
18156Z. N. Adelman, Applied Biosafety, 2021-01-07 18:05:08.
Advances in recombinant DNA approaches have resulted in the development of transgene architectures that severely bias their own inheritance, a process commonly referred to as ?gene drive.? The rapid pace of development, combined with the complexity of many gene drive approaches, threatens to overwhelm those responsible for ensuring its safe use in the laboratory, as even identifying that a specific transgene is capable of gene drive may not be intuitive. Although currently gene drive experiments have been limited to just a few species (mosquitoes, flies, mice, and yeast), the range of organisms used in gene drive research is expected to increase substantially in the coming years. Here the defining features of different gene drive approaches are discussed. Although this will start with a focus on identifying when gene drive could or could not occur, the emphasis will also be on establishing risk profiles based on anticipated level of invasiveness and persistence of transgenes in the surrounding environment. Attention is also called to the fact that transgenes can be considered invasive without being considered gene drive (and vice versa). This further supports the notion that adequate risk assessment requires information regarding the specific circumstances a given transgene or set of transgenes is capable of invading a corresponding population. Finally, challenges in the review and evaluation of work involving gene drive organisms are discussed.
Ubiquitous Selfish Toxin-Antidote Elements in Caenorhabditis Species
15947E. Ben-David, P. Pliota, S. A. Widen, A. Koreshova, T. Lemus-Vergara, P. Verpukhovskiy, S. Mandali, C. Braendle, A. Burga and L. Kruglyak, Current Biology, 2021-01-07 16:57:04.
Here, we report the discovery of maternal-effect TAs in both C. tropicalis and C. briggsae, two distant relatives of C. elegans. In C. tropicalis, multiple TAs combine to cause a striking degree of intraspecific incompatibility: five elements reduce the fitness of >70% of the F2 hybrid progeny of two Caribbean isolates. We identified the genes underlying one of the novel TAs, slow-1/grow-1, and found that its toxin, slow-1, is homologous to nuclear hormone receptors. Remarkably, although previously known TAs act during embryonic development, maternal loading of slow-1 in oocytes specifically slows down larval development, delaying the onset of reproduction by several days. Finally, we found that balancing selection acting on linked, conflicting TAs hampers their ability to spread in populations, leading to more stable genetic incompatibilities. Our findings indicate that TAs are widespread in Caenorhabditis species and target a wide range of developmental processes and that antagonism between them may cause lasting incompatibilities in natural populations. We expect that similar phenomena exist in other animal species.
Next-generation tools to control biting midge populations and reduce pathogen transmission
15940P. Shults, L. W. Cohnstaedt, Z. N. Adelman and C. Brelsfoard, Parasites and Vectors, 14:31. 2021-01-07 14:52:23.
Biting midges of the genus Culicoides transmit disease-causing agents resulting in a significant economic impact on livestock industries in many parts of the world. Localized control efforts, such as removal of larval habitat or pesticide application, can be logistically difficult, expensive and ineffective if not instituted and maintained properly. With these limitations, a population-level approach to the management of Culicoides midges should be investigated as a means to replace or supplement existing control strategies. Next-generation control methods such as Wolbachia- and genetic-based population suppression and replacement are being investigated in several vector species. Here we assess the feasibility and applicability of these approaches for use against biting midges. We also discuss the technical and logistical hurdles needing to be addressed for each method to be successful, as well as emphasize the importance of addressing community engagement and involving stakeholders in the investigation and development of these approaches.
