Keywords: synthetic homing drive

Double-tap gene drive uses iterative genome targeting to help overcome resistance alleles

A. L. Bishop, V. López Del Amo, E. M. Okamoto, Z. Bodai, A. C. Komor and V. M. Gantz,  Nat Commun,  13:2595. 2022.
Homing CRISPR gene drives could aid in curbing the spread of vector-borne diseases and controlling crop pest and invasive species populations due to an inheritance rate that surpasses Mendelian laws. However, this technology suffers from resistance alleles formed when the ...
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Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models

Y. Liu, W. Teo, H. Yang and J. Champer,  bioRxiv,  2022.05.08.491087. 2022.
Suppression gene drives are designed to bias their inheritance and increase in frequency in a population, disrupting an essential gene in the process. When the frequency is high enough, the population will be unable to reproduce above the replacement level and could be ...
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Cas9-mediated maternal-effect and derived resistance alleles in a gene-drive strain of the African malaria vector mosquito, Anopheles gambiae

R. Carballar-Lejarazú, T. Tushar, T. B. Pham and A. A. James,  Genetics,  2022.
CRISPR/Cas9 technologies are important tools for the development of gene-drive systems to modify mosquito vector populations to control the transmission of pathogens that cause diseases such as malaria. However, one of the challenges for current Cas9-based drive systems is their ...
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Finding the strongest gene drive: Simulations reveal unexpected performance differences between Anopheles homing suppression drive candidates

S. E. Champer, I. K. Kim, A. G. Clark, P. W. Messer and J. Champer,  bioRxiv,  2022.03.28.486009. 2022.
Recent experiments have produced several Anopheles gambiae homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such drives may be highly effective tools to combat malaria. One such homing drive, based on the zpg promoter ...
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Considerations for homology-based DNA repair in mosquitoes: Impact of sequence heterology and donor template source

J. X. D. Ang, K. Nevard, R. Ireland, D.-K. Purusothaman, S. A. N. Verkuijl, L. Shackleford, E. Gonzalez, M. A. E. Anderson and L. Alphey,  PLOS Genetics,  18:e1010060. 2022.
Author summary The field of genetic control of mosquito vectors has progressed rapidly in recent years, especially in Cas9-based control systems, due to its robustness to elicit a species-specific and dispersive control of mosquito population. To generate a Cas9-based ...
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Gene-drive mosquitoes, a prospect for future malaria control

S. A. Monawwer, A. O. I. Alzubaidi, F. Yasmin, S. M. Q. Haimour, S. M. I. Shay and I. Ullah,  Pan African Medical Journal,  41:2-6. 2022.
Despite major developments in malaria control over the past two decades, the disease continues to scourge the human population across the globe. Rising concerns such as insecticide resistance amongst vector mosquitoes are a cause of huge fear amongst healthcare providers and ...
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Gene drives for vertebrate pest control: realistic spatial modelling of eradication probabilities and times for island mouse populations

A. Birand, P. Cassey, J. V. Ross, J. C. Russell, P. Thomas and T. A. A. Prowse,  Molecular Ecology,  2022.
Abstract Invasive alien species continue to threaten global biodiversity. CRISPR-based gene drives, which can theoretically spread through populations despite imparting a fitness cost, could be used to suppress or eradicate pest populations. We develop an individual-based, ...
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Modeling CRISPR gene drives for suppression of invasive rodents using a supervised machine learning framework

S. E. Champer, N. Oakes, R. Sharma, P. García-Díaz, J. Champer and P. W. Messer,  PLoS Comput Biol,  17:e1009660. 2021.
Invasive rodent populations pose a threat to biodiversity across the globe. When confronted with these invaders, native species that evolved independently are often defenseless. CRISPR gene drive systems could provide a solution to this problem by spreading transgenes among ...
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Modeling impact and cost-effectiveness of driving-Y 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,  Evolutionary Applications,  2021.
Malaria elimination will be challenging in countries that currently continue to bear high malaria burden. Sex-ratio distorting gene drives, such as driving-Y, could play a role in an integrated elimination strategy if they can effectively suppress vector populations. Using a ...
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Demographic feedbacks can hamper the spatial spread of a gene drive

L. Girardin and F. Débarre,  Journal of Mathematical Biology,  83:67. 2021.
This paper is concerned with a reaction–diffusion system modeling the fixation and the invasion in a population of a gene drive (an allele biasing inheritance, increasing its own transmission to offspring). In our model, the gene drive has a negative effect on the fitness of ...
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CRISPR gene-drive systems based on Cas9 nickases promote super-Mendelian inheritance in Drosophila

V. Lopez del Amo, S. Sanz Juste and V. M. Gantz,  bioRxiv,  2021.12.01.470847. 2021.
CRISPR-based gene drive systems can be used to modify entire wild populations due to their ability to bias their own inheritance towards super-Mendelian rates (>100%). Current gene drives contain a Cas9 and a gRNA gene inserted at the location targeted by the gRNA. These ...
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Gene drives and population persistence vs elimination: the impact of spatial structure and inbreeding at low density

P. J. Beaghton and A. Burt,  bioRxiv,  2021.11.11.468225. 2021.
Synthetic gene drive constructs are being developed to control disease vectors, invasive species, and other pest species. In a well-mixed random mating population a sufficiently strong gene drive is expected to eliminate a target population, but it is not clear whether the same ...
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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.