Self-destructing mosquitoes and sterilized rodents: the promise of gene drives

Scudellari, Megan

doi:10.1038/d41586-019-02087-5

Cited by 55 publications

(37 citation statements)

References 13 publications

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“…Males carrying a non-driving I-PpoI construct designed to cause dominant male sterility 21 were recently released in a field location of Burkina Faso 24 as part of a phased, step-by-step assessment of novel genetic approaches to malaria control, following independent guidance and recommendations 25 , 26 . This opened the way to the use of an I-PpoI-based distorter for the implementation of genetic vector control measures.…”

Section: Discussionmentioning

confidence: 99%

A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae

et al. 2020

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ex-chromosome drivers are genetic elements that interfere with chromosome segregation during meiosis and are over-represented in progeny 1. In heterogametic sex, they cause an unbalanced male-to-female ratio among offspring, which can potentially lead to population suppression or extinction. Relatively few sex-chromosome drives have been characterized, most likely because they produce an evolutionary conflict with the rest of the genome that selects for autosomal suppressors or resistant sex chromosomes 2,3. Mathematical modeling predicts that a driving sex distorter will spread in a population and, in the absence of resistance, cause eventual collapse 4,5. Population collapse using natural sex-chromosome drives has been reported in laboratory colonies of Drosophila 6,7. In the field, a population crash of the species Drosophila neotestacea was detected in Washington State due to a natural X-chromosome distorter that produced a female-only population 8. Therefore, sex-distorter drives could conceivably be harnessed for invasive pest or vector control 9,10. Although Y drives are less common than X drives, they have been described in Aedes aegypti and Culex pipiens mosquitoes 11,12. Y drives are particularly attractive for mosquito vector control because they can progressively reduce the number of females and hence disease transmission as they spread. In addition, Y drives are likely to be more effective than X drives because they can increase at a greater rate the fraction of heterogametic driving individuals 3-5. Synthetic sex distorters have been generated in A. gambiae mosquitoes by using site-specific nucleases such as I-PpoI or CRISPR-Cas9, which cleave conserved repeated sequences in the mosquito ribosomal DNA gene cluster located exclusively on the X chromosome 13,14. These nucleases, when expressed during spermatozoa development, selectively cleave the X chromosome, thereby favoring the production of Y-bearing gametes and causing a 95% male bias in the progeny 13,14. However, attempts to convert synthetic sex-ratio distorters into Y-chromosome drives have been unsuccessful so far. In most insect species, including A. gambiae, the sex chromosomes are transcriptionally shut down during gametogenesis, a process known as meiotic sex-chromosome inactivation 15,16 , which prevents the transcription of X-shredding nucleases if they are inserted into the Y chromosome (personal observation, A.C. and R.G.). Recently, a gene drive that targeted the dsx gene reached 100% frequency in 7-11 generations and crashed a caged population of 600 mosquitoes without inducing resistance 17. We hypothesized that it might be possible to circumvent meiotic sex-chromosome inactivation by developing an autosomal male-biased sex distorter and coupling sex-ratio distortion with drive. This could result in a quicker impact on disease transmission and a synergistic effect (robustness) between the sex distorter and gene-drive components. Here we report the design and validation of an SDGD to spread the X-chromosome-shredding I-PpoI endonu...

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Section: Discussionmentioning

confidence: 99%

A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae

et al. 2020

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“…As a final note, the recent development of gene drives, notably in mosquitoes, have generated important ecological and biosafety concerns 45,46 . Our own work was conducted using laboratory viral strains unable to infect human hosts 47 , and there were therefore no risks of inadvertent release of gene drive viruses into the wild.…”

Section: Discussionmentioning

confidence: 99%

Viral gene drive in herpesviruses

Walter

Verdin

2020

Nat Commun

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Gene drives are genetic modifications designed to propagate in a population with high efficiency. Current gene drive strategies rely on sexual reproduction and are thought to be restricted to sexual organisms. Here, we report on a gene drive system that allows the spread of an engineered trait in populations of DNA viruses and, in particular, herpesviruses. We describe the successful transmission of a gene drive sequence between distinct strains of human cytomegalovirus (human herpesvirus 5) and show that gene drive viruses can efficiently target and replace wildtype populations in cell culture experiments. Moreover, by targeting sequences necessary for viral replication, our results indicate that a viral gene drive can be used as a strategy to suppress a viral infection. Taken together, this work offers a proof of principle for the design of a gene drive in viruses.

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“…There are additional concerns if genetically altered individuals are ever accidentally released or spread beyond their target areas of control (a hallmark of effective invaders), as gene drives are self‐sustaining (Noble et al ). Despite these justifiable concerns, plans are already underway to bring this technique to the field and to select an appropriate island for trials (Scudellari ). The use of the technique is clearly complex in terms of scientific, social, regulatory and ethical issues (Breed et al ), and it remains to be determined how effective gene drives will be over large geographic areas.…”

Section: Management and Eradicationmentioning

confidence: 99%

Genetic tools in the management of invasive mammals: recent trends and future perspectives

2020

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Invasive non‐native species are now considered to be one of the greatest threats to biodiversity worldwide. Therefore, efficient and cost‐effective management of species invasions requires robust knowledge of their demography, ecology and impacts, and genetic‐based techniques are becoming more widely adopted in acquiring such knowledge. We focus on the use of genetic tools in the applied management of mammalian invasions globally, as well as on their inherent advantages and disadvantages. We cover tools that are used in: 1) detecting and monitoring mammalian invaders; 2) identifying origins and invasive pathways; 3) assessing and quantifying the negative impacts of invaders; and 4) population management and potential eradication of invasive mammals. We highlight changes in sequencing technologies, including how the use of techniques such as Sanger sequencing and microsatellite genotyping, for monitoring and tracing invasive pathways respectively, are now giving way to the use of high‐throughput sequencing methods. These include the emergence of environmental DNA (eDNA) metabarcoding for the early detection of invasive mammals, and single nucleotide polymorphisms or whole genomes to trace the sources of invasive populations. We are now moving towards trials of genome‐editing techniques and gene drives to control or eradicate invasive rodents. Genetic tools can provide vital information that may not be accessible with non‐genetic methods, for the implementation of conservation policies (e.g. early detection using systematic eDNA surveillance, the identification of novel pathogens). However, the lack of clear communication of novel genetic methods and results (including transparency and reproducibility) to relevant stakeholders can be prohibitive in translating these findings to appropriate management actions. Geneticists should engage early with stakeholders to co‐design experiments in relation to management goals for invasive mammals.

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Self-destructing mosquitoes and sterilized rodents: the promise of gene drives

Cited by 55 publications

References 13 publications

A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae

A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae

Viral gene drive in herpesviruses

Genetic tools in the management of invasive mammals: recent trends and future perspectives

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