Keywords: gene drive models

Evading evolution of resistance to gene drives

R. Gomulkiewicz, M. L. Thies and J. J. Bull,  bioRxiv,  2020.08.27.270611. 2020.
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 this type would achieve only partial population suppression, but multiple drives (perhaps delivered ...
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Embracing Dynamic Models for Gene Drive Management

A. J. Golnar, E. Ruell, A. L. Lloyd and K. M. Pepin,  Trends in Biotechnology,  2020.
We describe how quantitative tools can reduce risk uncertainty, streamline empirical research, guide risk management, and promote cross-sector collaboration throughout the process of gene drive technology development and implementation.
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Gene Drive Dynamics in Natural Populations: The Importance of Density Dependence, Space, and Sex

S. Dhole, A. L. Lloyd and F. Gould,  Annual Review of Ecology, Evolution, and Systematics,  51:505-531. 2020.
The spread of synthetic gene drives is often discussed in the context of panmictic populations connected by gene flow and described with simple deterministic models. Under such assumptions, an entire species could be altered by releasing a single individual carrying an invasive ...
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Evading evolution of resistance to gene drives

R. Gomulkiewicz, M. L. Thies and J. J. Bull,  bioRxiv,  2020.
Here we develop mathematical and computational models to identify conditions under which suppression drives will evade resistance, even if resistance is present initially.
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Can a population targeted by a CRISPR-based homing gene drive be rescued?

N. O. Rode, V. Courtier-Orgogozo and F. Débarre,  G3-Genes Genomes Genetics,  2020.
N. O. Rode, V. Courtier-Orgogozo and F. Débarre (2020). G3 doi: 10.1534/g3.120.401484 Developing countermeasures is important to control the spread of gene drives, should they result in unanticipated damages. One proposed countermeasure is the introduction of individuals ...
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The potential for a CRISPR gene drive to eradicate or suppress globally invasive social wasps

P. J. Lester, M. Bulgarella, J. W. Baty, P. K. Dearden, J. Guhlin and J. M. Kean,  Scientific Reports,  10:12398. 2020.
P. J. Lester, M. Bulgarella, J. W. Baty, P. K. Dearden, J. Guhlin and J. M. Kean (2020). Scientific Reports. doi: 10.1038/s41598-020-69259-6 Gene drives have potential for widespread and cost-efficient pest control, but are highly controversial. We examined a potential gene ...
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Can CRISPR gene drive work in pest and beneficial haplodiploid species?

J. Li, O. Aidlin Harari, A.-L. Doss, L. L. Walling, P. W. Atkinson, S. Morin and B. E. Tabashnik,  Evolutionary Applications,  2020.
Gene drives based on CRISPR/Cas9 have the potential to reduce the enormous harm inflicted by crop pests and insect vectors of human disease, as well as to bolster valued species. In contrast with extensive empirical and theoretical studies in diploid organisms, little is known ...
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Simulation models from: Can CRISPER-mediated gene drive work in pest and beneficial haplodiploid species?

J. Li and B. Tabashnik,  Dryad,  2020.
Gene drives based on CRISPR/Cas9 have the potential to reduce the enormous harm inflicted by crop pests and insect vectors of human disease, as well as to bolster valued species. In contrast with extensive empirical and theoretical studies in diploid organisms, little is known ...
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Modeling confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit Aedes aegypti populations

H. M. Sánchez C, J. B. Bennett, S. L. Wu, G. Rašić, O. S. Akbari and J. M. Marshall,  BMC Biology,  18:50. 2020.
Here, we model hypothetical releases of two recently engineered threshold-dependent gene drive systems—reciprocal chromosomal translocations and a form of toxin-antidote-based underdominance known as UDMEL—to explore their ability to be confined and remediated.
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Gene drive dynamics in natural populations: The importance of density-dependence, space and sex

S. Dhole, A. L. Lloyd and F. Gould,  arXiv,  arXiv:2005.01838. 2020.
Here we review how different forms of density-dependence, spatial heterogeneity and mating behaviors can impact the spread of self-sustaining gene drives. We highlight specific aspects of gene drive dynamics and the target populations that need further research.
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Model Concepts for Gene Drive Dynamics

Johnannes L. Frieß, Merle Preu and Broder Breckling,  Gene Drives at Tipping Points,  2020.
The GeneTip project works on the conception and design modeling of population dynamics influenced by gene drives. In this pursuit, multiple different approaches and concepts have been developed to on one hand, be able to cover a broad perspective on the topic but on the other ...
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Case Study 1: Olive Fruit Fly (Bactrocera oleae)

Merle Preu, Johannes L. Frieß, Broder Breckling and Winfried Schröder,  Gene Drives at Tipping Points,  2020.
The olive fruit fly Bactrocera oleae is a phytophagous insect associated to olive trees (Olea europaea, Oleaceae). Its larvae monophagously feed on olive fruits, the fly is therefore considered the most severe pest of olive cultivation causing tremendous economic losses. The ...
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Can a population targeted by a CRISPR-based homing gene drive be rescued?

N. O. Rode, V. Courtier-Orgogozo and F. Débarre,  bioRxiv,  2020.03.17.995829. 2020.
CRISPR-based homing gene drive is a genetic control technique aiming to modify or eradicate natural populations through the release of individuals carrying an engineered piece of DNA that can be inherited by all their progeny. Developing countermeasures is important to control ...
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Computational and experimental performance of CRISPR homing gene drive strategies with multiplexed gRNAs

S. E. Champer, S. Y. Oh, C. Liu, Z. Wen, A. G. Clark, P. W. Messer and J. Champer,  Science Advances,  6:eaaz0525. 2020.
The rapid evolution of resistance alleles poses a major obstacle for genetic manipulation of populations with CRISPR homing gene drives. One proposed solution is using multiple guide RNAs (gRNAs), allowing a drive to function even if some resistant target sites are present. Here, ...
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Population-level multiplexing: A promising strategy to manage the evolution of resistance against gene drives targeting a neutral locus

M. P. Edgington, T. Harvey-Samuel and L. Alphey,  Evolutionary Applications,  10. 2020.
CRISPR-based gene drives bias inheritance in their favour by inducing double-stranded breaks (DSBs) at wild-type homologous loci and using the drive transgene as a repair template-converting drive heterozygotes into homozygotes. Recent studies have shown that alternate ...
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A unifying approach to gene drive

P. Verma, R. Reeves and C. S. Gokhale,  bioRxiv,  2020.02.28.970103. 2020.
Synthetic gene drive technologies aim to spread transgenic constructs into wild populations even when they impose organismal fitness disadvantages. The properties of gene drive constructs are diverse and depend on their molecular construction, and differential selection pressure ...
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Modeling the impacts of a simple meiotic gene drive on small, homeostatic populations

K. R. Pilkiewicz and M. L. Mayo,  Physical Review E,  101:11. 2020.
Gene drives offer unprecedented control over the fate of natural ecosystems by leveraging non-Mendelian inheritance mechanisms to proliferate synthetic genes across wild populations. However, these benefits are offset by a need to avoid the potentially disastrous consequences of ...
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Vector genetics, insecticide resistance and gene drives: an agent-based modeling approach to evaluate malaria transmission and elimination

P. Selvaraj, E. A. Wenger, D. Bridenbecker, N. Windbichler, J. R. Russell, J. Gerardin, C. A. Bever and M. Nikolov,  bioRxiv,  2020.01.27.920421. 2020.
Vector control has been a key component in the fight against malaria for decades, and chemical insecticides are critical to the success of vector control programs worldwide. However, increasing resistance to insecticides threatens to undermine these efforts. Understanding the ...
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A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment

V. López Del Amo, A. L. Bishop, H. M. Sánchez C, J. B. Bennett, X. Feng, J. M. Marshall, E. Bier and V. M. Gantz,  Nature Communications,  11:352. 2020.
CRISPR-based gene drives can spread through wild populations by biasing their own transmission above the 50% value predicted by Mendelian inheritance. These technologies offer population-engineering solutions for combating vector-borne diseases, managing crop pests, and ...
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Mathematical modeling of self-contained CRISPR gene drive reversal systems

M. G. Heffel and G. C. Finnigan,  Scientific Reports,  9:20050. 2019.
There is a critical need for further research into methods to control biological populations. Numerous challenges to agriculture, ecological systems, and human health could be mitigated by the targeted reduction and management of key species (e.g. pests, parasites, and vectors ...
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The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoes

Alcalay, Y., S. Fuchs, R. Galizi, F. Bernardini, R. E. Haghighat-Khah, D. B. Rusch, J. R. Adrion, M. W. Hahn, P. Tortosa and P. A. Papathanos,  bioRxiv,  2019:860551. 2019.
Synthetic sex-ratio distorters based on X-chromosome shredding are predicted to be more efficient than sterile males for population suppression of malaria mosquitoes using genetic control. X chromosome shredding operates through the targeted elimination of X-chromosome-bearing ...
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Design and analysis of CRISPR-based underdominance toxin-antidote gene drives

Champer, J., S. E. Champer, I. Kim, A. G. Clark and P. W. Messer,  bioRxiv,  861435:861435. 2019.
CRISPR gene drive systems offer a mechanism for transmitting a desirable transgene throughout a population for purposes ranging from vector-borne disease control to invasive species suppression. In this simulation study, we model and assess the performance of several CRISPR-based ...
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Fitness consequences of the selfish supergene Segregation Distorter

H. W. S. Wong and L. Holman,  Journal of Evolutionary Biology,  33:89-100. 2019.
Segregation distorters are selfish genetic elements that subvert Mendelian inheritance, often by destroying gametes that do not carry the distorter. Simple theoretical models predict that distorter alleles will either spread to fixation or stabilize at some high intermediate ...
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Evolutionary simulations of Z-linked suppression gene drives

L. Holman,  Proceedings of the Royal Society B-Biological Sciences,  286:1-9. 2019.
Synthetic gene drives may soon be used to suppress or eliminate populations of disease vectors, pathogens, invasive species, and agricultural pests. Recent proposals have focused on using Z-linked gene drives to control species with ZW sex determination, which include ...
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Threshold-Dependent Gene Drives in Wild Populations – A Podcast

G. A. Backus and J. A. Delborne,  BioScience Talks,  2019.
By altering the heritability of certain traits, gene drive technologies have the potential to spread desired genes through wild populations. In practice, this could lead to mosquito populations that, for example, bear traits making them resistant to the spread of malaria. Despite ...
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Threshold-Dependent Gene Drives in the Wild: Spread, Controllability, and Ecological Uncertainty

G. A. Backus and J. A. Delborne,  BioScience,  69:900-907. 2019.
Gene drive technology could allow the intentional spread of a desired gene throughout an entire wild population in relatively few generations. However, there are major concerns that gene drives could either fail to spread or spread without restraint beyond the targeted ...
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MGDrivE: A modular simulation framework for the spread of gene drives through spatially-explicit mosquito populations

Sánchez C, HMW, Sean L.; Bennett, Jared B.; Marshall, John M.,  Methods in Ecology and Evolution,  10:1-24. 2019.
Malaria, dengue, Zika, and other mosquito-borne diseases continue to pose a major global health burden through much of the world, despite the widespread distribution of insecticide-based tools and antimalarial drugs. The advent of CRISPR/Cas9-based gene editing and its ...
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Population management using gene drive: molecular design, models ofspread dynamics and assessment of ecological risks

Rode, NOE, A.; Bourguet, D.; Courtier-Orgogozo, V.; Debarre, F.,  Conservation Genetics,  20:671-690. 2019.
CRISPR gene drive has recently been proposed as a promising technology for population management, including in conservation genetics. The technique would consist in releasing genetically engineered individuals that are designed to rapidly propagate a desired mutation or transgene ...
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A Y-chromosome shredding gene drive for controlling pest vertebrate populations

Prowse, TAAA, F.; Cassey, P.; Thomas, P.; Ross, J. V.,  eLife,  8:19. 2019.
Self-replicating gene drives that modify sex ratios or infer a fitness cost could be used to control populations of invasive alien species. The targeted deletion of Y sex chromosomes using CRISPR technology offers a new approach for sex bias that could be incorporated within ...
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Predicting the spatial dynamics of Wolbachia infections in Aedes aegypti arbovirus vector populations in heterogeneous landscapes

Hancock, PAR, S. A.; Koenraadt, C. J. M.; Scott, T. W.; Hoffmann, A. A.; Godfray, H. C. J.,  Journal of Applied Ecology,  56:1674-1686. 2019.
A promising strategy for reducing the transmission of dengue and other arboviral human diseases by Aedes aegypti mosquito vector populations involves field introductions of the endosymbiotic bacteria Wolbachia. Wolbachia infections inhibit viral transmission by the mosquito, and ...
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Spatial structure undermines parasite suppression by gene drive cargo

Bull, JJR, Christopher H.; Gomulkiewicz, Richard; Krone, Stephen M.,  PeerJ,  7:e7921. 2019.
Gene drives may be used in two ways to curtail vectored diseases. Both involve engineering the drive to spread in the vector population. One approach uses the drive to directly depress vector numbers, possibly to extinction. The other approach leaves intact the vector population ...
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Modelling the potential of genetic control of malaria mosquitoes at national scale

North, ARB, Austin; Godfray, H. Charles J.,  BMC Biology,  17:26. 2019.
The persistence of malaria in large parts of sub-Saharan Africa has motivated the development of novel tools to complement existing control programmes, including gene-drive technologies to modify mosquito vector populations. Here, we use a stochastic simulation model to explore ...
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Daisy-chain gene drives for the alteration of local populations

Noble, CM, J.; Olejarz, J.; Buchthal, J.; Chavez, A.; Smidler, A. L.; DeBenedictis, E. A.; Church, G. M.; Nowak, M. A.; Esvelt, K. M.,  Proceedings of the National Academy of Sciences of the United States of America,  116:8275-8282. 2019.
If they are able to spread in wild populations, CRISPR-based gene-drive elements would provide new ways to address ecological problems by altering the traits of wild organisms, but the potential for uncontrolled spread tremendously complicates ethical development and use. Here, ...
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Integral gene drives for population replacement

Nash, AU, Giulia Mignini; Beaghton, Andrea K.; Hoermann, Astrid; Papathanos, Philippos Aris; Christophides, George K.; Windbichler, Nikolai,  Biology Open,  8:bio037762. 2019.
A first generation of CRISPR-based gene drives has now been tested in the laboratory in a number of organisms, including malaria vector mosquitoes. Challenges for their use in the area-wide genetic control of vector-borne disease have been identified, including the development of ...
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Large-cage assessment of a transgenic sex-ratio distortion strain on populations of an African malaria vector

Facchinelli, LN, A.; Collins, C.; Menichelli, M.; Persampieri, T.; Bucci, A.; Spaccapelo, R.; Crisanti, A.; Benedict, M.,  Parasites & Vectors,  12:70. 2019.
Novel transgenic mosquito control methods require progressively more realistic evaluation. The goal of this study was to determine the effect of a transgene that causes a male-bias sex ratio on Anopheles gambiae target populations in large insectary cages. Life history ...
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Modeling the mutation and reversal of engineered underdominance gene drives

Edgington, MPA, Luke S.,  Journal of Theoretical Biology,  479:14-21. 2019.
A range of gene drive systems have been proposed that are predicted to increase their frequency and that of associated desirable genetic material even if they confer a fitness cost on individuals carrying them. Engineered underdominance (UD) is such a system and, in one version, ...
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Gene drive for population genetic control: non-functional resistance and parental effects

Beaghton, AKH, Andrew; Nolan, Tony; Crisanti, Andrea; Burt, Austin,  Proceedings of the Royal Society B: Biological Sciences,  286:20191586. 2019.