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>
Making gene drive biodegradable
15687J. Zapletal, N. Najmitabrizi, M. Erraguntla, M. A. Lawley, K. M. Myles and Z. N. Adelman, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190804. 2020-12-28 15:02:10.
Here, we consider the inclusion of self-elimination mechanisms into the design of homing-based gene drive transgenes. This approach not only caused the excision of the gene drive transgene, but also generates a transgene-free allele resistant to further action by the gene drive. Strikingly, our models suggest that this mechanism, acting at a modest rate (10%) as part of a single-component system, would be sufficient to cause the rapid reversion of even the most robust homing-based gene drive transgenes, without the need for further remediation.
Vector dynamics influence spatially imperfect genetic interventions against disease
16547M. K. Yuksel, C. H. Remien, B. Karki, J. J. Bull and S. M. Krone, Evolution, Medicine, and Public Health, 9:1-10. 2020-12-27 16:20:40.
In spatially structured populations, imperfect coverage of the vector will leave pockets in which the parasite may persist. Movement by humans may disrupt this local persistence and facilitate eradication when these pockets are small, spreading parasite reproduction outside unprotected areas and into areas that block its reproduction. Here, we consider the sensitivity of this process to biological details: do simple generalities emerge that may facilitate interventions?We develop formal mathematical models of this process similar to standard Ross–Macdonald models, but (i) specifying spatial structure of two patches, with vector transmission blocked in one patch but not in the other, (ii) allowing temporary human movement (travel instead of migration) and (iii) considering two different modes of mosquito biting.We find that there is no invariant effect of disrupting spatial structure with travel.
Application of the Relationship-Based Model to Engagement for Field Trials of Genetically Engineered Malaria Vectors
15898A. Kormos, G. C. Lanzaro, E. Bier, G. Dimopoulos, J. M. Marshall, J. Pinto, A. Aguiar dos Santos, A. Bacar, H. Sousa Pontes Sacramento Rompão and A. A. James, The American Journal of Tropical Medicine and Hygiene, 2020-12-21 14:17:29.
Although guidelines and recommendations for engagement for gene drives have recently been described, we argue here that communities and stakeholders should lead the planning, development, and implementation phases of engagement. The RBM provides a new approach to the development of ethical, transparent, and effective engagement strategies for malaria control programs.
CRISPR/Cas9 knockout of female-biased genes AeAct-4 or myo-fem in Ae. aegypti results in a flightless phenotype in female, but not male mosquitoes
15617S. O’Leary and Z. N. Adelman, PLOS Neglected Tropical Diseases, 14:e0008971. 2020-12-18 16:05:35.
Author summary Ae. aegypti is the most important vector of arboviruses throughout the world, and new strategies are urgently needed to add to our existing arsenal of control methods to prevent or halt disease transmission. Importantly, only female Ae. aegypti mosquitoes transmit arboviruses due to their need for vertebrate blood to support egg production. Here, we identify several genes that are critical only for female mosquito flight; genetic ablation of each gene resulted in flightless females, but flying males. Importantly, the female flightless phenotype was completely penetrant (100%), and the use of sex-biased flight muscle proteins appeared to be conserved throughout mosquito evolution. These data could be used to support the development of novel genetic control approaches to reduce the number of biting females across a wide range of disease vector species.
Precise single base substitution in the shibire gene by CRISPR/Cas9-mediated homology directed repair in Bactrocera tryoni
16693A. Choo, E. Fung, I. Y. Chen, R. Saint, P. Crisp and S. W. Baxter, BMC Genetics, 21. 2020-12-18 15:58:10.
Here we introduce a known Drosophila melanogaster temperature sensitive embryonic lethal mutation into Bactrocera tryoni, a serious horticultural pest in Australia. A non-synonymous point mutation in the D. melanogaster gene shibire causes embryonic lethality at 29 degrees C and we successfully used CRISPR/Cas9 technology to recreate the orthologous shibire temperature sensitive-1 (shi(ts1)) mutation in B. tryoni. Genotypic analyses over three generations revealed that a high fitness cost was associated with the shi(ts1) mutant allele and shi(ts1) homozygotes were not viable at 21 degrees C, which is a more severe phenotype than that documented in D. melanogaster.ConclusionsWe have demonstrated the first successful use of CRISPR/Cas9 to introduce precise single base substitutions in an endogenous gene via homology-directed repair in an agricultural pest insect and this technology can be used to trial other conditional mutations for the ultimate aim of generating genetic sexing strains for SIT.
Gene Drive-Modified Organisms: Developing Practical Risk Assessment Guidance
15554Y. Devos, M. B. Bonsall, L. G. Firbank, J. Mumford, F. Nogué and E. A. Wimmer, Trends in Biotechnology, 2020-12-17 14:48:35.
Risk assessors, risk managers, developers, potential applicants, and other stakeholders at many levels discuss the need for new or further risk assessment guidance for deliberate environmental releases of gene drive-modified organisms. However, preparing useful and practical guidance entails challenges, to which we offer recommendations based on our experience drafting guidance.
A CRISPR endonuclease gene drive reveals two distinct mechanisms of inheritance bias
15480S. A. N. Verkuijl, E. González, J. X. D. Ang, M. Li, N. P. Kandul, M. Anderson, O. S. Akbari, M. Bonsall and L. Alphey, bioRxiv, 2020.12.15.421271. 2020-12-16 14:45:08.
In this study, we report the functioning of sds3, bgcn, and nup50 expressed Cas9 in an Aedes aegypti homing split drive system targeting the white gene. We report their inheritance biasing capability, propensity for maternal deposition, and zygotic/somatic expression. Additionally, by making use of the tight linkage of white to the sex-determining locus, we were able to elucidate mechanisms of inheritance bias. We find inheritance bias through homing in double heterozygous males, but find that a previous report of the same drive occurred through meiotic drive. We propose that other previously reported 'homing'design gene drives may in fact bias their inheritance through other mechanisms with important implications for gene drive design.Competing Interest StatementThe authors have declared no competing interest.
The Antiviral Small-Interfering RNA Pathway Induces Zika Virus Resistance in Transgenic Aedes aegypti
15482A. E. Williams, I. Sanchez-Vargas, W. R. Reid, J. Y. Lin, A. W. E. Franz and K. E. Olson, Viruses, 12:18. 2020-12-15 14:45:29.
We used CRISPR/Cas9 to re-target a previously characterized locus (Chr2:321382225) and engineered mosquitoes expressing an inverted repeat (IR) dsRNA against the NS3/4A region of the ZIKV genome. Small RNA analysis revealed that the IR effector triggered the mosquito's siRNA antiviral pathway in bloodfed females. Nearly complete (90%) inhibition of ZIKV replication was found in vivo in both midguts and carcasses at 7 or 14 days post-infection (dpi). Furthermore, significantly fewer transgenic mosquitoes contained ZIKV in their salivary glands (p = 0.001), which led to a reduction in the number of ZIKV-containing saliva samples as measured by transmission assay. Our work shows that Ae. aegypti innate immunity can be co-opted to engineer mosquitoes resistant to ZIKV.
Evading resistance to gene drives
15422R. Gomulkiewicz, M. L. Thies and J. J. Bull, bioRxiv, 2020.08.27.270611. 2020-12-12 15:44:15.
Our analyses suggest that among gene drives that cause moderate suppression, toxin-antidote systems are less apt to select for resistance than homing drives. Single drives of moderate effect might cause only moderate population suppression, but multiple drives (perhaps delivered sequentially) would allow arbitrary levels of suppression. The most favorable case for evolution of resistance appears to be with suppression homing drives in which resistance is dominant and fully suppresses transmission distortion; partial suppression by resistance heterozygotes or recessive resistance are less prone to resistance evolution. Given that it is now possible to engineer CRISPR-based gene drives capable of circumventing allelic resistance, this design may allow for the engineering of suppression gene drives that are effectively resistance-proof.
Polyandry blocks gene drive in a wild house mouse population
15390A. Manser, B. Konig and A. K. Lindholm, Nature Communications, 11:8. 2020-12-11 14:12:22.
Here, we study the impact of polyandry on a well-known gene drive, called t haplotype, in an intensively monitored population of wild house mice. First, we show that house mice are highly polyandrous: 47% of 682 litters were sired by more than one male. Second, we find that drive-carrying males are particularly compromised in sperm competition, resulting in reduced reproductive success. As a result, drive frequency decreased during the 4.5 year observation period. Overall, we provide the first direct evidence that the spread of a gene drive is hampered by reproductive behaviour in a natural population.
Interdisciplinary development of a standardized introduction to gene drives for lay audiences
15381C. E. Schairer, C. Triplett, A. Buchman, O. S. Akbari and C. S. Bloss, BMC Medical Research Methodology, 20:15. 2020-12-10 15:09:37.
While there is wide consensus that the public should be consulted about emerging technology early in development, it is difficult to elicit public opinion about innovations unfamiliar to lay audiences. We sought public input on a program of research on genetic engineering to control mosquito vectors of disease that is led by scientists at the University of California and funded by the U.S. Defense Advanced Research Projects Agency (DARPA). In preparation for this effort, we developed a series of narrated slideshows to prompt responses to the development of gene drive mosquito control strategies among lay people. We describe the development and content of these slideshows and evaluate their ability to elicit discussions among focus group participants.
X-linked meiotic drive can boost population size and persistence
16876C. Mackintosh, A. Pomiankowski and M. F. Scott, Genetics, 217:11. 2020-12-10 14:26:46.
Here, we find general conditions for the spread and fixation of X-linked alleles. Our conditions show that the spread of X-linked alleles depends on sex-specific selection and transmission rather than the time spent in each sex. Applying this logic to meiotic drive, we show that polymorphism is heavily dependent on sperm competition induced both by female and male mating behavior and the degree of compensation to gamete loss in the ejaculate size of drive males. We extend these evolutionary models to investigate the demographic consequences of biased sex ratios. Our results suggest driving X-alleles that invade and reach polymorphism (or fix and do not bias segregation excessively) will boost population size and persistence time by increasing population productivity, demonstrating the potential for selfish genetic elements to move sex ratios closer to the population-level optimum. However, when the spread of drive causes strong sex-ratio bias, it can lead to populations with so few males that females remain unmated, cannot produce offspring, and go extinct. This outcome is exacerbated when the male mating rate is low. We suggest that researchers should consider the potential for ecologically beneficial side effects of selfish genetic elements, especially in light of proposals to use meiotic drive for biological control.
A patent review on strategies for biological control of mosquito vector
15377K. Parihar, M. Telang and A. Ovhal, World Journal of Microbiology and Biotechnology, 36:23. 2020-12-09 20:28:33.
This paper presents a comprehensive technology overview of patent documents disclosing biological agents for mosquito control. The patent analysis revealed that comparable number of patent documents were filed in two technology categories: non-recombinant agents and genetically modified (GM) agents. In the category of non-recombinant agents, toxic peptides from microbes and biological consortia seemed to be the earliest technology noted right from the year 1965 whereas the patent filings for suppression of mosquito population using genetic modification techniques have emerged from the year 2000 onwards. The United States of America is the leading patent filing jurisdiction followed by China and the Great Britain. Academic institutes have filed higher number of patent applications as compared to private companies. University of Florida was found to be the leading patent filing entity and its patents were focused on suppression of vector population using techniques such as release of insects with dominant lethal (RIDL) and RNA interference (RNAi).
Engineering a Culturable Serratia symbiotica Strain for Aphid Paratransgenesis
19389K. M. Elston, J. Perreau, G. P. Maeda, N. A. Moran and J. E. Barrick, Applied Environmental Microbiology, 87. 2020-12-06 17:18:42.
Aphids are global agricultural pests and important models for bacterial symbiosis. To date, none of the native symbionts of aphids have been genetically manipulated, which limits our understanding of how they interact with their hosts. Serratia symbiotica CWBI-2.3(T) is a culturable, gut-associated bacterium isolated from the black bean aphid. Closely related Serratia symbiotica strains are facultative aphid endosymbionts that are vertically transmitted from mother to offspring during embryogenesis. We demonstrate that CWBI-2.3(T) can be genetically engineered using a variety of techniques, plasmids, and gene expression parts. Then, we use fluorescent protein expression to track the dynamics with which CWBI-2.3(T) colonizes the guts of multiple aphid species, and we measure how this bacterium affects aphid fitness. Finally, we show that we can induce heterologous gene expression from engineered CWBI-2.3(T) in living aphids. These results inform the development of CWBI-2.3(T) for aphid paratransgenesis, which could be used to study aphid biology and enable future agricultural technologies.IMPORTANCE Insects have remarkably diverse and integral roles in global ecosystems. Many harbor symbiotic bacteria, but very few of these bacteria have been genetically engineered. Aphids are major agricultural pests and an important model system for the study of symbiosis. This work describes methods for engineering a culturable aphid symbiont, Serratia symbiotica CWBI-2.3(T) These approaches and genetic tools could be used in the future to implement new paradigms for the biological study and control of aphids.
Does RNAi-Based Technology Fit within EU Sustainability Goals?
C. N. T. Taning, B. Mezzetti, G. Kleter, G. Smagghe and E. Baraldi, Trends in Biotechnology, 2020-12-05 14:03:11.The Farm-to-Fork (F2F) strategyi, one of the pillars underneath the European Commission’s new Green Deal, aims to ensure a more sustainable and food-secure society. Its aims include a reduction in agrochemical inputs, such as pesticides, fertilizers, and antimicrobials, to achieve greater sustainability and health, and reduce loss of biodiversity while ensuring continued crop protection. It envisages various practices that promote lesser pesticide usage, such as integrated pest management (IPM), and the use of precision agriculture and artificial intelligence.
Targeting female flight for genetic control of mosquitoes
15310D. Navarro-Payá, I. Flis, M. A. E. Anderson, P. Hawes, M. Li, O. S. Akbari, S. Basu and L. Alphey, PLOS Neglected Tropical Diseases, 14:e0008876. 2020-12-03 20:11:01.
The yellow fever mosquito and the Southern house mosquito are important vectors of infectious diseases. Given their widespread presence across tropical and subtropical regions of the world and the increased risk of spread due to global warming there is a growing need for population control. Gene drives aim to spread a genetic element within target genes required for mosquito reproduction to disrupt their function and crash a population. Female-specific genes provide interesting candidates for population control since female mosquitoes determine the reproductive capacity of a population as well as being the actual vectors of disease. Here we describe a study on Actin-4 loss in both Aedes aegypti and Culex quinquefasciatus, where we observe female-specific disruption of flight ability and propose it as a candidate for genetic methods of population suppression.
Evaluating Gene Drive Approaches for Public Benefit
15296M. R. Santos, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:14:49.
Gene drive approaches—those which bias inheritance of a genetic element in a population of sexually reproducing organisms—have the potential to provide important public benefits. The spread of selected genetic elements in wild populations of organisms may help address certain challenges, such as transmission of vector-borne human and animal diseases and biodiversity loss due to invasive animals. Adapting various naturally occurring gene drive mechanisms to these aims is a long-standing research area, and recent advances in genetics have made engineering gene drive systems significantly more technically feasible. Gene drive approaches would act through changes in natural environments, thus robust methods to evaluate potential research and use are important.
Engineered Gene Drives and their Value in the Control of Vector-Borne Diseases, Weeds, Pests, and Invasive Species
15294K. Hefferon and R. Herring, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:10:55.
Genetic engineering has created potential for moving medical and agricultural research and application frontiers forward in unprecedented ways. Despite its accepted use as a powerful tool in medical research, genetic modification and genome editing technologies remain controversial in large-scale ecological intervention and open-field agriculture. Gene drive is a technology based on genome editing that enables a trait to be pushed through a given population at a greater than expected rate. While gene drives show enormous promise as a way to address a number of challenges, such as the reduction of populations of disease-spreading pests and invasive species, they also incite great social unease because of unknown risks. The following chapter describes the mechanics of gene drives and how they could be utilized to control vector-borne diseases, weeds, and crop pests and even protect populations of endangered species. Limitations and risks associated with gene drive technologies, such as containment strategies and potential resistance, are discussed. Finally, the social impacts of gene drives with respect to international governance and public acceptance are considered.
Engineered Gene Drives: Ecological, Environmental, and Societal Concerns
15292J. Kuzma, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:07:26.
This chapter overviews the types, purposes, and potential impacts of gene drive organisms (GDOs) and discusses challenges with foreseeing and assessing these impacts prior to their environmental release. It concludes with a few examples of risk analysis methods and governance systems that scholars have proposed to cope with the novelty of GDOs and uncertainties associated with their use. With GDOs poised for release in the near future, it is urgent that technologists, ecologists, social scientists, ethicists, stakeholders, and publics work together to grapple with the immense challenges associated with assessments of GDOs and the design of governance systems to ensure their responsible development and potential use.
Genetically Engineered Fish: Potential Impacts on Aquaculture, Biodiversity, and the Environment
15290R. A. Dunham and B. Su, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:03:48.
Studies on transgenic fish for the aquaculture industry have focused on improving growth rates, enhancing disease resistance, altering body composition, acting as biological factories for medical proteins, and even altering temperature tolerance and coloration. The future impact of transgenesis will likely be quite large. Growth hormone-transgenic salmon has been approved for human consumption and has been introduced to the market in Canada and soon to the USA. This is the first human consumption of approved transgenic meat. Transgene insertion has many pleiotropic effects. Several studies have projected the fitness of transgenic fish to be low, in general, compared to non-transgenic and wild fish; thus, their environmental risk is likely low and they would have minimal, if any, long-term impact on ecosystems or biodiversity. However, there have been no actual escapements; thus, only projections of risk are available based on small-scale experiments and the characteristics of transgenic fish compared to controls. An active area of research is repressible transgenic sterilization and sterilization using gene editing, both of which would allow application of transgenic fish with only short-term consequences for ecosystems in the worst-case scenario. Transgenic technology could also be potentially used to reduce or eliminate populations of nuisance species.
Contact Us
Alex Sullivan
Foundation for the
National Institutes of Health
geneconvenevi@fnih.org