Keywords: synthetic homing drive

Targeting Conserved Sequences Circumvents the Evolution of Resistance in a Viral Gene Drive against Human Cytomegalovirus

M. Walter, R. Perrone, E. Verdin and F. Goodrum,  Journal of Virology,  95:e00802-21. 2021.
Gene drives are genetic systems designed to efficiently spread a modification through a population. They have been designed almost exclusively in eukaryotic species, especially in insects. We recently developed a CRISPR-based gene drive system in herpesviruses that relies on ...
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Experimental demonstration of tethered gene drive systems for confined population modification or suppression

M. Metzloff, E. Yang, S. Dhole, A. G. Clark, P. W. Messer and J. Champer,  bioRxiv,  2021.05.29.446308. 2021.
Tethered drive systems, in which a locally confined gene drive provides the CRISPR nuclease needed for a homing drive, could provide a solution to this problem, offering the power of a homing drive and confinement of the supporting drive. Here, we demonstrate the engineering of a ...
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Ultra-conserved sequences in the genomes of highly diverse Anopheles mosquitoes, with implications for malaria vector control

S. M. O'Loughlin, A. J. Forster, S. Fuchs, T. Dottorini, T. Nolan, A. Crisanti and A. Burt,  G3-Genes Genomes Genetics,  2021.
Here we search for conserved sequences of 18bp and over in an alignment of 21 Anopheles genomes, spanning an evolutionary timescale of 100 million years, and characterise the resulting sequences according to their location and function. Over 8000 ultra-conserved elements were ...
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Gene-Editing Approach To Control the Invasive Gray Squirrel

M. Campbell,  Technology Networks,  2021.
Biodiversity refers to the extent of the variety of life that is found on planet Earth – and it is currently under threat. Changes in biodiversity have been flagged as "surpassing safe limits" for several years, and world leaders and scientists across the globe are consequently ...
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A confinable home and rescue gene drive for population modification

N. P. Kandul, J. Liu, J. B. Bennett, J. M. Marshall and O. S. Akbari,  eLife,  10:e65939. 2021.
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 ...
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Ecology: Gene drives may help control invasive grey squirrel in the UK

A. Korn,  EurekaAlert,  2021.
Gene drives introduce genes into a population that have been changed to induce infertility in females, allowing for the control of population size. However, they face technical challenges, such as controlling the spread of altered genes as gene drive individuals mate with wild ...
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Genetically modified squirrels could curb growing population of greys

S. Knapton,  Telegraph,  2021.
Mutant grey squirrels, genetically modified to spread infertility genes, could be released into the wild to tackle the burgeoning population,
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Expert reaction to a paper suggesting that gene drives could be used to help control grey squirrel numbers in the UK

Anonymous,  Science Media Centre,  2021.
This study assesses the prospects for using a gene drive to control invasive grey squirrels in the UK. This is a modelling study exploring the potential for such an approach – no such gene drives currently exist and developing them for grey squirrels would be quite a long-term ...
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CRISPR gene drives may come to a squirrel near you.

Anonymous,  NewsBeezer,  2021.
Today’s gene drive technologies could be blended to provide control of the invasive gray squirrel population in the UK – with minimal risk to other populations, according to a new modeling published in the journal Scientific reports. Gene driving introduces altered genes ...
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Novel combination of CRISPR-based gene drives eliminates resistance and localises spread

N. R. Faber, G. R. McFarlane, R. C. Gaynor, I. Pocrnic, C. B. A. Whitelaw and G. Gorjanc,  Scientific Reports,  11:3719. 2021.
As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and economic losses. HD-ClvR combats resistance allele formation by combining a homing gene drive with a cleave-and-rescue gene ...
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Designing gene drives to limit spillover to non-target populations

G. Greenbaum, M. W. Feldman, N. A. Rosenberg and J. Kim,  PLOS Genetics,  17:e1009278. 2021.
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 ...
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Modeling impact and cost-effectiveness of gene drives for malaria elimination in the Democratic Republic of the Congo

N. Metchanun, C. Borgemeister, G. Amzati, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin,  medRxiv,  2020.06.29.20142760. 2021.
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 ...
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Regulating the expression of gene drives is key to increasing their invasive potential and the mitigation of resistance

A. 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.
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.
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Control of malaria-transmitting mosquitoes using gene drives

T. Nolan,  Philosophical Transactions of the Royal Society B: Biological Sciences,  376:20190803. 2020.
In this article, I will discuss the relative merits of this type of gene drive, as well as barriers to its technical development and to its deployment in the field as malaria control. This article is part of the theme issue ‘Novel control strategies for mosquito-borne ...
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Evading 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 moderate effect might cause only moderate population suppression, but multiple drives (perhaps delivered ...
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Split drive killer-rescue provides a novel threshold-dependent gene drive

M. P. Edgington, T. Harvey-Samuel and L. Alphey,  Scientific Reports,  10. 2020.
Population genetics mathematical models are developed here to demonstrate the threshold-dependent nature of the proposed system and its robustness to imperfect homing, incomplete penetrance of toxins and transgene fitness costs, each of which are of practical significance given ...
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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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Gene Drive: The What, How, Why, and Whether We Should

N. Pazhayam,  The Pipettepen,  2020.
Under regular Mendelian inheritance, the probability of inheriting a particular allele from a heterozygous parent is 50% – this is because offspring can only inherit one or the other chromosome from each parent. However, gene drive is a technology that changes this probability ...
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Progress Toward Zygotic and Germline Gene Drives in Mice

C. Pfitzner, M. A. White, S. G. Piltz, M. Scherer, F. Adikusuma, J. N. Hughes and P. Q. Thomas,  The CRISPR Journal,  3:388-397. 2020.
Here, we investigated the efficiency of CRISPR-Cas9-based gene drives in Mus musculus by constructing "split drive" systems where gRNA expression occurs on a separate chromosome to Cas9, which is under the control of either a zygotic (CAG) or germline (Vasa) promoter.
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MGDrivE 2: A simulation framework for gene drive systems incorporating seasonality and epidemiological dynamics

S. L. Wu, J. B. Bennett, H. M. Sanchez C, A. J. Dolgert, T. M. Leon and J. M. Marshall,  bioRxiv,  2020.10.16.343376. 2020.
We present MGDrivE 2 (Mosquito Gene Drive Explorer 2): an extension of and development from the MGDrivE 1 simulation framework that investigates the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations.
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Engineered Gene Drives: State of Research Webinar Series by The GeneConvene Global Collaborative September-October 2020

David O'Brochta and Hector Quemada,  GeneConvene Global Collaborative,  2020.
A series of technical webinars on engineered gene drive technology research and development given by leading researchers in the field.
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Engineering the Composition and Fate of Wild Populations with Gene Drive

B. A. Hay, G. Oberhofer and M. Guo,  Annual Review of Entomology,  2020.
We describe technologies under consideration, progress that has been made, and remaining technological hurdles, particularly with respect to evolutionary stability and our ability to control the spread and ultimate fate of genes introduced into populations.
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Assessing the acoustic behaviour of Anopheles gambiae (s.l.) dsxF mutants: implications for vector control

M. P. Su, M. Georgiades, J. Bagi, K. Kyrou, A. Crisanti and J. T. Albert,  Parasites and Vectors,  13:507. 2020.
We analysed sound emissions and acoustic preference in a doublesex mutant previously used to collapse Anopheles gambiae (s.l.) cages.
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Viral gene drive in herpesviruses

M. Walter and E. Verdin,  Nature Communications,  11:4884. 2020.
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.
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Gene Drive Control Worry Eased by Genetic Neutralizing Elements

Staff,  Genetic Engineering and Biotechnology News,  2020.
Bier and his colleagues have developed two new active genetic systems that address such risks by halting or eliminating gene drives in the wild, offering two new solutions based on elements developed in the common fruit fly. T
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Active Genetic Neutralizing Elements for Halting or Deleting Gene Drives

X.-R. S. Xu, E. A. Bulger, V. M. Gantz, C. Klanseck, S. R. Heimler, A. Auradkar, J. B. Bennett, L. A. Miller, S. Leahy, S. S. Juste, A. Buchman, O. S. Akbari, J. M. Marshall and E. Bier,  Molecular Cell,  2020.
Here we describe two self-copying (or active) guide RNA-only genetic elements, called e-CHACRs and ERACRs. These elements use Cas9 produced in trans by a gene drive either to inactivate the cas9 transgene (e-CHACRs) or to delete and replace the gene drive (ERACRs).
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Biologists create new genetic systems to neutralize gene drives

University of California San Diego,  ScienceDaily,  2020.
Now, scientists at the University of California San Diego and their colleagues have developed two new active genetic systems that address such risks by halting or eliminating gene drives in the wild.
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A CRISPR homing gene drive targeting a haplolethal gene removes resistance alleles and successfully spreads through a cage population

J. Champer, E. Yang, E. Lee, J. Liu, A. G. Clark and P. W. Messer,  Proceedings of the National Academy of Sciences,  202004373. 2020.
Here, we present a CRISPR homing drive that was able to successfully spread to all individuals in a laboratory cage study in Drosophila melanogaster without any apparent evolution of resistance.
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Inherently confinable split-drive systems in Drosophila

G. Terradas, A. B. Buchman, J. B. Bennett, I. Shriner, J. M. Marshall, O. S. Akbari and E. Bier,  bioRxiv,  2020.09.03.282079. 2020.
Here, we test split gene-drive (sGD) systems in Drosophila melanogaster that were inserted into essential genes required for viability (rab5, rab11, prosalpha2) or fertility (spo11). I
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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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Novel combination of CRISPR-based gene drives eliminates resistance and localises spread

N. R. Faber, G. R. McFarlane, R. C. Gaynor, I. Pocrnic, C. B. A. Whitelaw and G. Gorjanc,  bioRxiv,  2020.
We present HD-ClvR, a novel combination of CRISPR-based gene drives that eliminates resistance and localises spread. As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and ...
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Anthony James / Mosquito Modification

Big Picture Science,  SETI Institute,  2020.
Anthony James, vector biologist at the University of California, Irvine, describeshow we might genetically modify mosquitoes to make them unable to pass malaria on to humans.
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Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae

R. Carballar-Lejarazú, C. Ogaugwu, T. Tushar, A. Kelsey, T. B. Pham, J. Murphy, H. Schmidt, Y. Lee, G. C. Lanzaro and A. A. James,  Proceedings of the National Academy of Sciences,  202010214. 2020.
We show here that the Cas9/guide RNA-based gene-drive components of a genetically-engineered malaria mosquito vector, Anopheles gambiae, achieve key target product profile requirements for efficacy and performance.
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A home and rescue gene drive forces its inheritance stably persisting in populations

N. P. Kandul, J. Liu, J. B. Bennett, J. M. Marshall and O. Akbari,  bioRxiv,  2020.08.21.261610. 2020.
We demonstrate that HomeR can achieve nearly ~100% transmission enabling it to persist at genotypic fixation in several multi-generational population cage experiments, underscoring its long term stability.
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Modelling the suppression of a malaria vector using a CRISPR-Cas9 gene drive to reduce female fertility

A. R. North, A. Burt and H. C. J. Godfray,  BMC Biology,  18:98. 2020.
Gene drives based on CRISPR-Cas9 technology are increasingly being considered as tools for reducing the capacity of mosquito populations to transmit malaria, and one of the most promising options is driving endonuclease genes that reduce the fertility of female mosquitoes. Here, ...
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CRISPR gene drives could eliminate many vector-driven pests and diseases, but challenges remain

J. Champer,  Genetic Literacy Project,  2020.
A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, ...
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Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

A. Adolfi, V. M. Gantz, N. Jasinskiene, H.-F. Lee, K. Hwang, E. A. Bulger, A. Ramaiah, J. B. Bennett, G. Terradas, J. J. Emerson, J. M. Marshall, E. Bier and A. A. James,  bioRxiv,  2020.08.02.233056. 2020.
We developed the first recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional ...
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Chemical controllable gene drive in Drosophila

D. Chae, J. Lee, N. Lee, K. Park, S. J. Moon and H. H. Kim,  ACS Synthetic Biology,  in press. 2020.
Here, we report a chemical-induced control of gene drive. We prepared a CRISPR-based gene drive system that can be removed by a site-specific recombinase, Rippase, the expression of which is induced by the chemical RU486 in fruit flies. Exposure of fruit flies to RU486 resulted ...
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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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Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives

V. López Del Amo, B. S. Leger, K. J. Cox, S. Gill, A. L. Bishop, G. D. Scanlon, J. A. Walker, V. M. Gantz and A. Choudhary,  Cell Reports,  31:107841. 2020.
Summary Synthetic CRISPR-based gene-drive systems have tremendous potential in public health and agriculture, such as for fighting vector-borne diseases or suppressing crop pest populations. These elements can rapidly spread in a population by breaching the inheritance limit of ...
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Role of gene drives in malaria elimination strategy: modeling impact and cost-effectiveness in the Democratic Republic of the Congo

N. Metchanun, C. Borgemeister, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin,  medRxiv,  2020.
The tremendous burden of malaria has led to renewed efforts on malaria elimination and the development of novel tools for application where existing tools fall short. Gene drive mosquitoes, where transgenes and their associated phenotypes are efficiently propagated to future ...
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Development of zygotic and germline gene drives in mice

C. Pfitzner, J. N. Hughes, M. A. White, M. Scherer, S. G. Piltz and P. Q. Thomas,  bioRxiv,  2020.
Here we investigated the efficiency of CRISPR/Cas9-based gene drives in Mus musculus by constructing "split drive" systems with Cas9 under the control of zygotic (CAG) or germline (Vasa) promoters.
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Detecting the population dynamics of an autosomal sex ratio distorter transgene in malaria vector mosquitoes

P. Pollegioni, A. R. North, T. Persampieri, A. Bucci, R. L. Minuz, D. A. Groneberg, T. Nolan, P. A. Papathanos, A. Crisanti and R. Muller,  Journal of Applied Ecology,  11. 2020.
A sex-distorting autosomal transgene has been developed recently in G3 mosquitoes, a laboratory strain of the malaria vectorAnopheles gambiaes.l. Following the World Health Organization guidance framework for the testing of GM mosquitoes, we assessed the dynamics of this ...
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Fighting malaria with gene-drive technology

EarthWise,  earthwise radio,  2020.
A team led by Imperial College London has created a genetic modification that distorts the sex ratio of a population of Anopheles gambiae mosquitoes using “gene drive” technology. The modification works by using a DNA-cutting enzyme to destroy the X chromosome during the ...
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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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A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae

A. Simoni, A. M. Hammond, A. K. Beaghton, R. Galizi, C. Taxiarchi, K. Kyrou, D. Meacci, M. Gribble, G. Morselli, A. Burt, T. Nolan and A. Crisanti,  Nature Biotechnology,  2020.
We report a male-biased sex-distorter gene drive (SDGD) in the human malaria vector Anopheles gambiae.
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