Keywords: synthetic homing drive
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Next-generation CRISPR gene-drive systems using Cas12a nucleaseS. Sanz Juste, E. M. Okamoto, X. Feng and V. L. Del Amo, bioRxiv, 2023.02.20.529271. 2023.
One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a ... |
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Next-generation CRISPR gene-drive systems using Cas12a nucleaseS. Sanz Juste, E. M. Okamoto, X. Feng and V. L. Del Amo, bioRxiv, 2023.02.20.529271. 2023.
One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a ... |
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Modeling the efficacy of CRISPR gene drive for snail immunity on schistosomiasis controlR. E. Grewelle, J. Perez-Saez, J. Tycko, E. K. O. Namigai, C. G. Rickards and G. A. De Leo, PLOS Neglected Tropical Diseases, 16:e0010894. 2022.
CRISPR gene drives could revolutionize the control of infectious diseases by accelerating the spread of engineered traits that limit parasite transmission in wild populations. Gene drive technology in mollusks has received little attention despite the role of freshwater snails as ... |
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Assessing single-locus CRISPR/Cas9-based gene drive variants in the mosquito Aedes aegypti via single generation crosses and modelingW. Reid, A. E. Williams, I. Sanchez-Vargas, J. Lin, R. Juncu, K. E. Olson and A. W. E. Franz, G3 Genes|Genomes|Genetics, 2022.
Critical to the design of a single-locus autonomous GD is that the selected genomic locus is amenable to both GD and appropriate expression of the antiviral effector. In our study, we used reverse engineering to target two intergenic genomic loci, which had previously shown to be ... |
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Anopheles homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial structureS. E. Champer, I. K. Kim, A. G. Clark, P. W. Messer and J. Champer, eLife, 11:e79121. 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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A theory of resistance to multiplexed gene drive demonstrates the significant role of weakly deleterious natural genetic variationB. S. Khatri and A. Burt, Proceedings of the National Academy of Sciences, 119:e2200567119. 2022.
CRISPR-based gene drives have the potential for controlling natural populations of disease vectors, such as malaria-carrying mosquitoes in sub-Saharan Africa. If successful, they hold promise of significantly reducing the burden of disease and death from malaria and many other ... |
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A population modification gene drive targeting both Saglin and Lipophorin disables Plasmodium transmission in Anopheles mosquitoesE. I. Green, E. Jaouen, D. Klug, R. P. Olmo, A. Gautier, S. A. Blandin and E. Marois, bioRxiv, 2022.07.08.499187. 2022.
Lipophorin is an essential, highly expressed lipid transporter protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles gambiae Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria ... |
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Genetic Approaches for Controlling CRISPR-based Autonomous Homing Gene DrivesP. R. Chennuri, Z. N. Adelman and K. M. Myles, Frontiers in Bioengineering and Biotechnology, 10:897231. 2022.
CRISPR-based autonomous homing gene drives are a potentially transformative technology with the power to reduce the prevalence of, or even eliminate, vector-borne diseases, agricultural pests, and invasive species. However, there are a number of regulatory, ethical, ... |
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Double-tap gene drive uses iterative genome targeting to help overcome resistance allelesA. 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 modelsY. 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 gambiaeR. 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 candidatesS. 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 sourceJ. 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 controlS. 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 populationsA. 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 frameworkS. 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 CongoN. 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 driveL. 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 DrosophilaV. 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 densityP. 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 CytomegalovirusM. 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 suppressionM. 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 controlS. 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 SquirrelM. 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 modificationN. 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 UKA. 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 greysS. 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 UKAnonymous, 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 spreadN. 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 populationsG. 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 CongoN. 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 resistanceA. 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 drivesT. 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 drivesR. 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 driveM. 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 drivesR. 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 ShouldN. 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 MiceC. 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 dynamicsS. 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 2020David 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 DriveB. 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 controlM. 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 herpesvirusesM. 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 ElementsStaff, 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 DrivesX.-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 drivesUniversity 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 populationJ. 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 DrosophilaG. 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 drivesR. 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 spreadN. 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 ModificationBig 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 gambiaeR. 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 populationsN. 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 fertilityA. 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 remainJ. 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 stephensiA. 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 DrosophilaD. 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 waspsP. 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 DrivesV. 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 CongoN. 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 miceC. 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 mosquitoesP. 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 technologyEarthWise, 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 gambiaeA. 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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Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacementA. Hoermann, S. Tapanelli, P. Capriotti, E. K. G. Masters, T. Habtewold, G. K. Christophides and N. Windbichler, bioRxiv, 2020.
Here we explore how minimal genetic modifications of endogenous mosquito genes can convert them directly into non-autonomous gene drives without disrupting their expression. |
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Genetic Biocontrol – An OverviewGeneConvene Global Collaborative,, GeneConvene Global Collaborative, 2020.
This video explains what genetic biocontrol is and surveys various technologies that can be consider genetic biocontrol technologies. It offers a conceptual organization of the various technologies based on the potential of genetic biocontrol organisms to persist and spread in ... |
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Gene Drive Basics – Characteristics and PropertiesGeneConvene Global Collaborative, GeneConvene Global Collaborative, 2020.
This short video covers the concept of 'drive strength', 'drive thresholds', 'spreading', 'resistance' and describes two strategies by which transmission advantages can be achieved. The video is intended to provide additional insights into the technology to enable and encourage ... |
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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 gRNAsS. 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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Anti-CRISPR protein applications: natural brakes for CRISPR-Cas technologiesMarino, N. D., Pinilla-Redondo, R. , Csorgo, B., Bondy-Denomy, J., Nature Methods, 2020.
Clustered, regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) genes, a diverse family of prokaryotic adaptive immune systems, have emerged as a biotechnological tool and therapeutic. The discovery of protein inhibitors of CRISPR-Cas systems, ... |
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Performance analysis of novel toxin-antidote CRISPR gene drive systemsJ. Champer, I. K. Kim, S. E. Champer, A. G. Clark and P. W. Messer, BMC Biology, 18:27. 2020.
CRISPR gene drive systems allow the rapid spread of a genetic construct throughout a population. Such systems promise novel strategies for the management of vector-borne diseases and invasive species by suppressing a target population or modifying it with a desired trait. ... |
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Progress towards engineering gene drives for population controlR. R. Raban, J. M. Marshall and O. S. Akbari, The Journal of Experimental Biology, 223:jeb208181. 2020.
Vector-borne diseases, such as dengue, Zika and malaria, are a major cause of morbidity and mortality worldwide. These diseases have proven difficult to control and currently available management tools are insufficient to eliminate them in many regions. Gene drives have the ... |
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Gene technologies in weed management: a technical feasibility analysisN. Kumaran, A. Choudhary, M. Legros, A. W. Sheppard, L. G. Barrett, D. M. Gardiner and S. Raghu, Current Opinion in Insect Science, 38:6-14. 2020.
With the advent of new genetic technologies such as gene silencing and gene drive, efforts to develop additional management tools for weed management is gaining significant momentum. These technologies promise novel ways to develop sustainable weed control options because gene ... |
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A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deploymentV. 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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The kill-switch for CRISPR that could make gene-editing saferE. Dolgin, Nature, 577:308-310. 2020.
How anti-CRISPR proteins and other molecules could bolster biosecurity and improve medical treatments. |
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Assessment of a Split Homing Based Gene Drive for Efficient Knockout of Multiple GenesN. P. Kandul, J. Liu, A. Buchman, V. M. Gantz, E. Bier and O. S. Akbari, G3: Genes|Genomes|Genetics, 10:827-837. 2019.
Homing based gene drives (HGD) possess the potential to spread linked cargo genes into natural populations and are poised to revolutionize population control of animals. Given that host encoded genes have been identified that are important for pathogen transmission, targeting ... |
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Experimental population modification of the malaria vector mosquito, Anopheles stephensiT. B. Pham, C. H. Phong, J. B. Bennett, K. Hwang, N. Jasinskiene, K. Parker, D. Stillinger, J. M. Marshall, R. Carballar-Lejarazú and A. A. James, PLOS Genetics, 15:e1008440. 2019.
The experimental introduction of manipulated genes into insect species has a long history in basic genetics. Recent advances in genome editing technologies have spurred considerable effort to exploit these methodologies to provide genetic solutions to some of the worst medical ... |
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The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoesAlcalay, 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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Plasmodium falciparum (Haemosporodia: Plasmodiidae) and O’nyong-nyong virus development in a transgenic Anopheles gambiae (Diptera: Culicidae) strainMumford, J. D., C. A. Long, S. C. Weaver, K. Miura, E. Wang, R. Rotenberry, E. M. Dotson and M. Q. Benedict, " Journal of Medical Entomology, 56:936-941. 2019.
ransgenic Anopheles gambiae Giles (Diptera: Culicidae) mosquitoes have been developed that confer sexual sterility on males that carry a transgene encoding a protein which cuts ribosomal DNA. A relevant risk concern with transgenic mosquitoes is that their capacity to transmit ... |
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A bacterial gene-drive system efficiently edits and inactivates a high copy number antibiotic resistance locusValderrama, J. A., S. S. Kulkarni, V. Nizet and E. Bier, Nature Communications, 10:5726. 2019.
Gene-drive systems in diploid organisms bias the inheritance of one allele over another. CRISPR-based gene-drive expresses a guide RNA (gRNA) into the genome at the site where the gRNA directs Cas9-mediated cleavage. In the presence of Cas9, the gRNA cassette and any linked cargo ... |
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Genetic Control of MosquitoesAlphey, L., Annual Review of Entomology, 59:205-224. 2019.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their ... |
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Antibiotic resistance hoops countered by gene drive feedback loopsGEN, Genetic Engineering & Biotechnology News, 2019.
Where a gene drive that cuts and destroys plasmids may fail, a gene drive that cuts, pastes, and copies plasmids may succeed. The “where,” in this case, is an antibiotic-resistant bacterium that carries multiple copies of an antibiotic-resistance gene. That is, the target ... |
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Tackling antibiotic resistance head-on with CRISPRThomas, L., News Medical Life Sciences, 2019.
With modern advances in genetic engineering occurring almost every day, the latest discovery concerns antibiotic resistance. Using the powerful gene editor CRISPR, scientists reported the development of a gene-drive system that is 100 times as efficient as other current systems ... |
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The bold plan to end malaria with a gene driveVOX, , 2019.
How genetically engineered mosquitoes might defeat a disease that kills millions of children. This describes gene drive and features work from a group (Target Malaria) that is developing this technology for use against malaria |
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A Controversial Swarm Of Genetically Modified Mosquitoes In A Lab In ItalyNPR, , 2019.
An international team of scientists is conducting a controversial experiment in Italy. The experiment is designed to test genetically modified mosquitoes that researchers hope could provide a powerful new weapon to fight malaria, which remains one of the world's greatest ... |
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Viral gene drive in herpesvirusesWalter, M. and E. Verdin, bioRxiv, 2019:717017. 2019.
Herpesviruses are ubiquitous pathogens in need of novel therapeutic solutions. Current engineered gene drive strategies rely on sexual reproduction, and are thought to be restricted to sexual organisms. Here, we report on the design of a novel gene drive system that allows the ... |
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Assessment of a split homing based gene drive for efficient knockout of multiple genesKandul, N. P., J. Liu, A. Buchman, V. M. Gantz, E. Bier and O. S. Akbari, bioRxiv, 2019:706929. 2019.
Homing based gene drives (HGD) possess the potential to spread linked cargo genes into natural populations and are poised to revolutionize population control of animals. Given that host-encoded genes have been identified that are important for pathogen transmission, targeting ... |
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Self-destructing mosquitoes and sterilized rodents: the promise of gene drivesM. Scudellari, Nature, 571:160-162. 2019.
Altering the genomes of entire animal populations could help to defeat disease and control pests, but researchers worry about the consequences of unleashing this new technology. |
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Split-gene drive system provides flexible application for safe laboratory investigation and potential field deploymentV. L. Del Amo, A. L. Bishop, H. M. Sánchez C, J. B. Bennett, X. Feng, J. M. Marshall, E. Bier and V. M. Gantz, bioRxiv, 684597. 2019.
CRISPR-based gene drives spread through populations bypassing the dictates of Mendelian genetics, offering a population-engineering tool for tackling vector-borne diseases, managing crop pests, and helping island conservation efforts; unfortunately, current technologies raise ... |
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Daisy-chain gene drivesMIT Media Lab, , 2019.
Who should decide whether, when, and how to alter the environment? These are hard questions, especially when the decisions will impact people in many different communities or nations. Daisy drive systems may help by empowering local communities to make decisions concerning their ... |
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MGDrivE: A modular simulation framework for the spread of gene drives through spatially-explicit mosquito populationsSánchez 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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Molecular safeguarding of CRISPR gene drive experimentsChamper, JC, Joan; Lee, Yoo Lim; Liu, Chen; Yang, Emily; Wen, Zhaoxin; Clark, Andrew G.; Messer, Philipp W., eLife, 8:e41439. 2019.
CRISPR-based homing gene drives have sparked both enthusiasm and deep concerns due to their potential for genetically altering entire species. This raises the question about our ability to prevent the unintended spread of such drives from the laboratory into a natural population. ... |
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Gene Drive – EsveltiBiology, , 2019.
Dr. Kevin Esvelt explains how CRISPR-based gene drives can be used to spread genetic alterations through wild populations. He discusses strategies to maximize benefit and minimize risk. |
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Design, execution, and analysis of CRISPR-Cas9-based deletions and genetic interaction networks in the fungal pathogen Candida albicansHalder, VP, C. B. M.; Chavez, A.; Shapiro, R. S., Nature Protocols, 14:955-975. 2019.
The study of fungal pathogens is of immediate importance, yet progress is hindered by the technical challenges of genetic manipulation. For Candida species, their inability to maintain plasmids, unusual codon usage, and inefficient homologous recombination are among the obstacles ... |
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Efficient allelic-drive in DrosophilaGuichard, AH, T.; Bobik, M.; Xu, X. R. S.; Klanseck, C.; Kushwah, R. B. S.; Berni, M.; Kaduskar, B.; Gantz, V. M.; Bier, E., Nature Communications, 10:1640. 2019.
Gene-drive systems developed in several organisms result in super-Mendelian inheritance of transgenic insertions. Here, we generalize this "active genetic" approach to preferentially transmit allelic variants (allelic-drive) resulting from only a single or a few nucleotide ... |
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Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9-mediated mutagenesis of the multiple edematous wings gene induces muscle weakness and flightlessness in Bactrocera dorsalis (Diptera: Tephritidae)Zheng, WL, Q.; Sun, H.; Ali, M. W.; Zhang, H., Insect Molecular Biology, 28:222-234. 2019.
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system is a versatile, efficient and heritable gene editing tool that can be useful for genome engineering. Bactrocera dorsalis (Hendel) is a major pest of agriculture that causes ... |
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Efficient somatic and germline genome engineering of Bactrocera dorsalis by the CRISPR/Cas9 systemZhao, STX, Z. Z.; Liu, Z. G.; Liu, Y. H.; Liu, X. R.; Chen, Z.; Li, J. H.; Yan, R. H., Pest Management Science, 75:1921-1932. 2019.
Bactrocera dorsalis (Hendel), a very destructive insect pest of many fruits and vegetables, is widespread in many Asian countries. To facilitate control of this pest, it is essential to investigate its genetics and gene function using targeted gene disruption. RESULTS Here, we ... |
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Daisy-chain gene drives for the alteration of local populationsNoble, 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 replacementNash, 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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Evaluating the Probability of CRISPR-based Gene Drive Contaminating Another SpeciesCourtier-Orgogozo, VD, Antoine; Gouyon, Pierre-Henri; Boëte, Christophe, bioRxiv, 776609:27. 2019.
The probability D that a given CRISPR-based gene drive element contaminates another, non-target species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: D = (hyb+transf).express.cut.flank.immune.nonextinct withhyb = probability of ... |
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Population Engineering | Gene Drive by CRISPR-CAS9SciToons, , 2018.
The CRISPR-CAS9 genome editing technology is opening up previously inconceivable possibilities for the manipulation of organisms. Our ethical discussion appears to be far behind the pace of technological development. In this new SciToons video, we address how CRISPR-CAS9 can be ... |
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CRISPR Gene Drive (Complete guide 2019)Every Cell A Universe, , 2018.
Crispr gene drive - malaria cure and a new way to look at conservation. |
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Multiple loci of small effect confer wide variability in efficiency and resistance rate of CRISPR gene driveJ. Champer, Z. Wen, A. Luthra, R. Reeves, J. Chung, C. Liu, Y. L. Lee, J. Liu, E. Yang, P. W. Messer and A. G. Clark, bioRxiv, 447615. 2018.
Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. CRISPR homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles ... |
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Malaria mosquitoes wiped out in lab trials of gene drive testingKelland, K, The Wire, 2018.
London: Scientists have succeeded in wiping out a population of caged mosquitoes in laboratory experiments using a type of genetic engineering known as a gene drive, which spread a modification blocking female reproduction.; ; The researchers, whose work was published on Monday ... |
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Gene drives could wipe out mosquitoesNew Scientist, , 2018.
This is a short video describing how gene drive is being considered for controlling malaria transmitting mosquitoes in Africa as part of ongoing malaria eradication efforts. |
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Gene drives breakthrough needs urgent restraintSteinbrecher, R, GMWatch, 2018.
Gene drive researchers associated with Target Malaria and funded by US DARPA, the GATES Foundation and the UK BBSRC have just managed to crash a population of caged mosquitoes after 7-11 generations.(1); ; This is a first, and it has brought this technology beyond the proof of ... |
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Here’s the Plan to End Malaria With Crispr-Edited MosquitoesMolteni, M, Wired, 2018.
In 2003, scientists at London’s Imperial College hatched a somewhat out-there idea. They wanted to deal with the increasingly pesticide-resistant mosquitoes that were killing half a million people a year by spreading malaria in sub-Saharan Africa. What biologists Austin Burt ... |
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The ethical implications of population suppression and the irreversibility of gene drivesJ. Kim, International Journal of Life Sciences Research, 2018.
This paper aims to examine the current situation by presenting important ethical arguments that include Chardin’s principle of irreversibility and Weiss’ beliefs on intergenerational equity, ideals upheld by the United Nations |
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Population modification of Anopheline species to control malaria transmissionR. Carballar-Lejarazú and A. A. James, Pathogens and Global Health, 111:424-435. 2018.
Vector control strategies based on population modification of Anopheline mosquitoes may have a significant role in the malaria eradication agenda. They could consolidate elimination gains by providing barriers to the reintroduction of parasites and competent vectors, and allow ... |
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Economic issues to consider for gene drivesP. D. Mitchell, Z. Brown and N. McRoberts, Journal of Responsible Innovation, 5:S180-S202. 2018.
We examine four economic issues regarding gene drive applications made possible by gene editing technologies. The potentially substantial benefits, coupled with the technical, social, and economic uncertainties surrounding gene drives, suggest that a responsible course of action ... |
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Identifying and detecting potentially adverse ecological outcomes associated with the release of gene-drive modified organismsK. R. Hayes, G. R. Hosack, G. V. Dana, S. D. Foster, J. H. Ford, R. Thresher, A. Ickowicz, D. Peel, M. Tizard, P. De Barro, T. Strive and J. M. Dambacher, Journal of Responsible Innovation, 5:S139-S158. 2018.
In this paper, we outline methods to identify hazards and detect potentially adverse ecological outcomes at the individual (genotype, phenotype), population, community and ecosystem level, when progressing Gene Drive Modified Organisms through a phased test and release pathway. ... |
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Developing gene drive technologies to eradicate invasive rodents from islandsC. M. Leitschuh, D. Kanavy, G. A. Backus, R. X. Valdez, M. Serr, E. A. Pitts, D. Threadgill and J. Godwin, Journal of Responsible Innovation, 5:S121-S138. 2018.
Gene drive methods of rodent eradication offer an alternative to killing that has the potential to be more species-specific, more humane, and more biologically safe for use around humans. Implementing this technology would involve releasing laboratory-developed engineered mice ... |
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Agricultural production: assessment of the potential use of Cas9-mediated gene drive systems for agricultural pest controlM. J. Scott, F. Gould, M. Lorenzen, N. Grubbs, O. Edwards and D. O’Brochta, Journal of Responsible Innovation, 5:S98-S120. 2018.
To highlight how gene drives could be useful for control of agricultural insect pests, we selected species that are pests of animals (New World screwworm), plants (spotted wing Drosophila, diamondback moth, Bemisia tabaci whitefly), or stored grains (red flour beetle). We ... |
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Gene drive to reduce malaria transmission in sub-Saharan AfricaA. Burt, M. Coulibaly, A. Crisanti, A. Diabate and J. K. Kayondo, Journal of Responsible Innovation, 5:S66-S80. 2018.
Gene drive is a natural process by which some genes are inherited at a greater-than-Mendelian rate and can spread through a population even if they cause harm to the organisms carrying them. Many different synthetic gene drive systems have been proposed to suppress the number of ... |
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Gene drive to reduce malaria transmission in sub-Saharan AfricaBurt, AC, Mamadou; Crisanti, Andrea; Diabate, Abdoulaye; Kayondo, Jonathan K., Journal of Responsible Innovation, 5:S66-S80. 2018.
Despite impressive progress, malaria continues to impose a substantial burden of mortality and morbidity, particularly in sub-Saharan Africa, and new tools will be needed to achieve elimination. Gene drive is a natural process by which some genes are inherited at a ... |
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Pathway to deployment of gene drive mosquitoes as a potential biocontrol tool for elimination of malaria in sub-Saharan Africa: Recommendations of a scientific working groupJames, SC, Frank H.; Welkhoff, Philip A.; Emerson, Claudia; Godfray, H. Charles J.; Gottlieb, Michael; Greenwood, Brian; Lindsay, Steve W.; Mbogo, Charles M.; Okumu, Fredros O.; Quemada, Hector; Savadogo, Moussa; Singh, Jerome A.; Tountas, Karen H.; Touré, American Journal of Tropical Medicine and Hygiene, 98:1-49. 2018.
Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic ... |
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Gene drive inhibition by the anti-CRISPR proteins AcrIIA2 and AcrIIA4 in Saccharomyces cerevisiaeBasgall, EMG, S. C.; Goeckel, M. E.; Giersch, R. M.; Roggenkamp, E.; Schrock, M. N.; Halloran, M.; Finnigan, G. C., Microbiology-Sgm, 164:464-474. 2018.
Given the widespread use and application of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas gene editing system across many fields, a major focus has been the development, engineering and discovery of molecular means to precisely control and regulate ... |
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Improved CRISPR-based suppression gene drives mitigate resistance and impose a large reproductive load on laboratory-contained mosquito populationsHammond, AMK, Kyros; Gribble, Matthew; Karlsson, Xenia; Morianou, Ioanna; Galizi, Roberto; Beaghton, Andrea; Crisanti, Andrea; Nolan, Tony, bioRxiv, 360339:1-16. 2018.
CRISPR-based genes drives bias their own inheritance and can be used to modify entire populations of insect vectors of disease as a novel form of sustainable disease control. Gene drives designed to interfere with female fertility can suppress populations of the mosquito vector ... |
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A CRISPR–Cas9-based gene drive platform for genetic interaction analysis in Candida albicansShapiro, RSC, Alejandro; Porter, Caroline B. M.; Hamblin, Meagan; Kaas, Christian S.; DiCarlo, James E.; Zeng, Guisheng; Xu, Xiaoli; Revtovich, Alexey V.; Kirienko, Natalia V.; Wang, Yue; Church, George M.; Collins, James J., Nature Microbiology, 3:73-82. 2018.
Candida albicans is the leading cause of fungal infections; yet, complex genetic interaction analysis remains cumbersome in this diploid pathogen. Here, we developed a CRISPR–Cas9-based ‘gene drive array’ platform to facilitate efficient genetic analysis in C. albicans. In ... |
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CRISPR-based gene drives for pest controlMcFarlane, GRW, C. Bruce A.; Lillico, Simon G., Trends in Biotechnology, 36:130-133. 2018.
Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene drives (GDs) could be used to spread desirable genetic elements through wild populations. With the imminent development of this technology in vertebrates, we believe that it is timely to highlight two ... |
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Invasion and migration of spatially self-limiting gene drives: A comparative analysisDhole, S.; Vella, M. R; Lloyd, A. L.; Gould, F., Evolutionary Applications, 11:794-808. 2018.
Recent advances in research on gene drives have produced genetic constructs that could theoretically spread a desired gene (payload) into all populations of a species, with a single release in one place. This attribute has advantages, but also comes with risks and ethical ... |
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Can CRISPR-based gene drive be confined in the Wild? A question for molecular and population biologyMarshall, JMA, Omar S., ACS Chemical Biology, 13:424-430. 2018.
The recent discovery of CRISPR and its application as a gene editing tool has enabled a range of gene drive systems to be engineered with greater ease. In order for the benefits of this technology to be realized, in some circumstances drive systems should be developed that are ... |
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Development of a multi-locus CRISPR gene drive system in budding yeastYan, YF, Gregory C., Scientific reports, 8:17277-17277. 2018.
The discovery of CRISPR/Cas gene editing has allowed for major advances in many biomedical disciplines and basic research. One arrangement of this biotechnology, a nuclease-based gene drive, can rapidly deliver a genetic element through a given population and studies in fungi and ... |
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Tuning CRISPR-Cas9 gene grives in Saccharomyces cerevisiaeRoggenkamp, EG, Rachael M.; Schrock, Madison N.; Turnquist, Emily; Halloran, Megan; Finnigan, Gregory C., G3-Genes Genomes Genetics, 8:999. 2018.
Control of biological populations is an ongoing challenge in many fields, including agriculture, biodiversity, ecological preservation, pest control, and the spread of disease. In some cases, such as insects that harbor human pathogens (e.g., malaria), elimination or reduction of ... |
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Reducing resistance allele formation in CRISPR gene driveChamper, JL, Jingxian; Oh, Suh Yeon; Reeves, Riona; Luthra, Anisha; Oakes, Nathan; Clark, Andrew G.; Messer, Philipp W., Proceedings of the National Academy of Sciences of the United States of America, 115:5522-5527. 2018.
A functioning gene drive mechanism could fundamentally change our strategies for the control of vector-borne diseases, such as malaria, dengue, and Zika. CRISPR homing gene drive promises such a mechanism, which could be used to rapidly spread genetic modifications among the ... |
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The use of driving endonuclease genes to suppress mosquito vectors of malaria in temporally variable environmentsLambert, BN, Ace; Burt, Austin; Godfray, H. Charles J., Malaria Journal, 17:154. 2018.
The use of gene drive systems to manipulate populations of malaria vectors is currently being investigated as a method of malaria control. One potential system uses driving endonuclease genes (DEGs) to spread genes that impose a genetic load. Previously, models have shown that ... |
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A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoesKyrou, KH, Andrew M.; Galizi, Roberto; Kranjc, Nace; Burt, Austin; Beaghton, Andrea K.; Nolan, Tony; Crisanti, Andrea, Nature Biotechnology, 36:1062–1066. 2018.
In the human malaria vector Anopheles gambiae, the gene doublesex (Agdsx) encodes two alternatively spliced transcripts, dsx-female (AgdsxF) and dsx-male (AgdsxM), that control differentiation of the two sexes. The female transcript, unlike the male, contains an exon (exon 5) ... |
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Correction to ‘Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates’Prowse, TAAC, Phillip; Ross, Joshua V.; Pfitzner, Chandran; Wittmann, Talia; Thomas, Paul, Proceedings of the Royal Society B: Biological Sciences, 285:1-2. 2018.
Proc. R. Soc. B 284, 20170799. (Published Online 9 August 2017). (doi:10.1098/rspb.2017.0799)We recently found an error in our calculation of the probability of a wild-type allele moving from s to j susceptible sites (), and acquiring the gene drive (), during gene-drive homing, ... |
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Consequences of resistance evolution in a Cas9-based sex conversion-suppression gene drive for insect pest managementCarrami, Eli M., ME, Kolja N.; Ahmed, Hassan M. M.; Sánchez C., Héctor M.; Dippel, Stefan; Marshall, John M.; Wimmer, Ernst A., Proceedings of the National Academy of Sciences of the United States of America, 115:6189-6194. 2018.
Resistance evolution caused by CRISPR/Cas9 gene-drive systems has a major impact on both the future scientific design of such gene-drive systems and on the politics of regulating experimentation and use of such systems. In our study, we show that in-frame drive-resistant alleles ... |
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Gene Drives Explained – Questions about Gene DrivesQuestion., , 2017.
Hi, thanks for watching on the channel Question, where we seek to better understand scientific breakthroughs by asking and answering questions. Today’s video topic is on gene drives - a way to increase the frequency of an allele in a population. Gene drives work hand in hand ... |
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Using CRISPR-based gene drive for agriculture pest controlV. Courtier-Orgogozo, B. Morizot and C. Boëte, EMBO Reports, 18:1481. 2017.
The authors respond to comments to their publication 10.15252/embr.201744205 |
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Agricultural pest control with CRISPR-based gene drive: time for public debateV. Courtier-Orgogozo, B. Morizot and C. Boëte, EMBO Reports, 18:878-880. 2017.
Gene drive technology to control disease vectors or pests has great potential for addressing humanitarian and public health problems. Its application for pest control in agriculture, however, raises important environmental, social and ethical issues. |
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Gene drive for Malaria control | Andrea Crisanti |TEDx, , 2017.
Andrea discusses his team's laboratory work that has developed a revolutionary technology to spread genetic modifications from few laboratory mosquitoes to wild populations to eradicate malaria in the near future |
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Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebratesProwse, TAAC, Phillip; Ross, Joshua V.; Pfitzner, Chandran; Wittmann, Talia A.; Thomas, Paul, Proceedings of the Royal Society B: Biological Sciences, 284:20170799. 2017.
Self-replicating gene drives that can spread deleterious alleles through animal populations have been promoted as a much needed but controversial ‘silver bullet’ for controlling invasive alien species. Homing-based drives comprise an endonuclease and a guide RNA (gRNA) that ... |
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How driving endonuclease genes can be used to combat pests and disease vectorsGodfray, HCJN, A.; Burt, A., BMC Biology, 15:81. 2017.
Driving endonuclease genes (DEGs) spread through a population by a non-Mendelian mechanism. In a heterozygote, the protein encoded by a DEG causes a double-strand break in the homologous chromosome opposite to where its gene is inserted and when the break is repaired using the ... |
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Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamicsEckhoff, PAW, E. A.; Godfray, H. C. J.; Burt, A., Proceedings of the National Academy of Sciences of the United States of America, 114:e255-e264. 2017.
The renewed effort to eliminate malaria and permanently remove its tremendous burden highlights questions of what combination of tools would be sufficient in various settings and what new tools need to be developed. Gene drive mosquitoes constitute a promising set of tools, with ... |
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CRISPR/Cas9 gene drives in genetically variable and nonrandomly mating wild populationsDrury, DWD, A. L.; Siniard, D. J.; Zentner, G. E.; Wade, M. J., Science Advances, 3:e1601910. 2017.
Synthetic gene drives based on CRISPR/Cas9 have the potential to control, alter, or suppress populations of crop pests and disease vectors, but it is unclear how they will function in wild populations. Using genetic data from four populations of the flour beetle Tribolium ... |
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Gene drives do not always increase in frequency: from genetic models to risk assessmentde Jong, TJ, Journal Fur Verbraucherschutz Und Lebensmittelsicherheit-Journal of Consumer Protection and Food Safety, 12:299-307. 2017.
Homing genes encode endonucleases that make a double stranded break in the DNA, destroying a target site on the homologous chromosome. When the cell repairs the break the homing allele is copied, converting a heterozygote into a homozygote. This results in gene drive (GD), an ... |
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Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populationsChamper, JR, Riona; Oh, Suh Yeon; Liu, Chen; Liu, Jingxian; Clark, Andrew G.; Messer, Philipp W., PLOS Genetics, 13:e1006796. 2017.
Author summary Gene drive systems provide a wide array of potential applications, including new strategies for the control of vector-borne diseases. For example, a functioning gene drive system could rapidly spread a genetically modified allele designed to reduce pathogen ... |
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Evolution of Resistance Against CRISPR/Cas9 Gene DriveUnckless, RLC, A. G.; Messer, P. W., Genetics, 205:827-841. 2017.
CRISPR/Cas9 gene drive (CGD) promises to be a highly adaptable approach for spreading genetically engineered alleles throughout a species, even if those alleles impair reproductive success. CGD has been shown to be effective in laboratory crosses of insects, yet it remains ... |
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New Weapons in the Toad Toolkit: A Review of Methods to Control and Mitigate the Biodiversity Impacts of Invasive Cane Toads (Rhinella Marina)Tingley, RW-F, Georgia; Schwarzkopf, Lin; Greenlees, Matthew J.; Phillips, Benjamin L.; Brown, Gregory; Clulow, Simon; Webb, Jonathan; Capon, Robert; Sheppard, Andy; Strive, Tanja; Tizard, Mark; Shine, Richard, The Quarterly Review of Biology, 92:123-149. 2017.
Our best hope of developing innovative methods to combat invasive species is likely to come from the study of high-profile invaders that have attracted intensive research not only into control, but also basic biology. Here we illustrate that point by reviewing current thinking ... |
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Results from the Workshop “Problem Formulation for the Use of Gene Drive in Mosquitoes”Roberts, ADA, P. P.; Okumu, F.; Quemada, H.; Savadogo, M.; Singh, J. A.; James, S., American Journal of Tropical Medicine and Hygiene, 96:530-533. 2017.
Reducing the incidence of malaria has been a public health priority for nearly a century. New technologies and associated vector control strategies play an important role in the prospect of sustained reductions. The development of the CRISPR/Cas9 gene editing system has generated ... |
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The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquitoHammond, AMK, Kyros; Bruttini, Marco; North, Ace; Galizi, Roberto; Karlsson, Xenia; Kranjc, Nace; Carpi, Francesco M.; D’Aurizio, Romina; Crisanti, Andrea; Nolan, Tony, PLOS Genetics, 13:e1007039. 2017.
Gene drives are selfish genetic elements that are able to bias their own inheritance among offspring. Starting from very low frequencies they can rapidly invade a population in just a few generations, even when imposing a fitness cost. Gene drives based on the precise DNA cutting ... |
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CRISPR/Cas9 gene drive: Growing pains for a new technologyReed, FA, Genetics, 205:1037-1039. 2017.
In this commentary, Floyd Reed discusses Unckless et al. (2017),; “Evolution of resistance against CRISPR/Cas9 gene drive,”; which was published in the February issue of GENETICS. |
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Potential of gene drives with genome editing to increase genetic gain in livestock breeding programsGonen, SJ, J.; Gorjanc, G.; Mileham, A. J.; Whitelaw, C. B. A.; Hickey, J. M., Genetics Selection Evolution, 49:14. 2017.
This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. Methods: We simulated nine ... |
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Gene Drives: Saving Lives Or Powering Extinctions?Fw:Thinking, , 2016.
A few months back we talked about the revolutionary gene-editing technique known as CRISPR-Cas9 – a technology based on the bacterial immune system that will allow us to make edits to an organism’s genetic code with more ease and accuracy than ever before. CRISPR is changing ... |
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Lethal Gene Drive Selects InbreedingJ. J. Bull, bioRxiv, 046847. 2016.
ere, population genetic models are used to consider the evolution of inbreeding (specifically selfing) as a possible response to a recessively lethal HEG with complete segregation distortion. Numerical analyses indicate a rich set of outcomes, but selfing often evolves in ... |
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Gene editing can now change an entire species — foreverTED, , 2016.
CRISPR gene drives allow scientists to change sequences of DNA and guarantee that the resulting edited genetic trait is inherited by future generations, opening up the possibility of altering entire species forever. More than anything, this technology has led to questions: How ... |
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A CRISPR-Cas9 gene drive system-targeting female reproduction in the malaria mosquito vector Anopheles gambiaeHammond, AG, R.; Kyrou, K.; Simoni, A.; Siniscalchi, C.; Katsanos, D.; Gribble, M.; Baker, D.; Marois, E.; Russell, S.; Burt, A.; Windbichler, N.; Crisanti, A.; Nolan, T., Nature Biotechnology, 34:78-83. 2016.
Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for ... |
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Cas9-triggered chain ablation of cas9 as a gene drive brakeWu, BL, L. Q.; Gao, X. J. J., Nature Biotechnology, 34:137-138. 2016.
We designed and synthesized a transgene system that we named Cas9-triggered chain ablation (CATCHA). The CATCHA transgene encodes a guide RNA (gRNA) that is expressed ubiquitously from a U6:2 promoter. The gRNA targets a site within the DNA sequence of cas9. The guide RNA is ... |
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The dawn of active geneticsGantz, VMB, E., Bioessays, 38:50-63. 2016.
On December 18, 2014, a yellow female fly quietly emerged from her pupal case. What made her unique was that she had only one parent carrying a mutant allele of this classic recessive locus. Then, one generation later, after mating with a wild-type male, all her offspring ... |
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CRISPR-Cas9: Safeguarding Gene DrivesHarvard University, , 2015.
In this animation, learn how effective safeguarding mechanisms developed at the Wyss Institute and Harvard Medical School can be applied to ensure gene drive research is done responsibly in the laboratory. These safeguards enable responsible scientific investigation into how gene ... |
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Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensiGantz, VMJ, N.; Tatarenkova, O.; Fazekas, A.; Macias, V. M.; Bier, E.; James, A. A., Proceedings of the National Academy of Sciences of the United States of America, 112:e6736-e6743. 2015.
Genetic engineering technologies can be used both to create transgenic mosquitoes carrying antipathogen effector genes targeting human malaria parasites and to generate gene-drive systems capable of introgressing the genes throughout wild vector populations. We developed a highly ... |
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The mutagenic chain reaction: A method for converting heterozygous to homozygous mutationsGantz, VMB, Ethan, Science, 348:442. 2015.
Loss-of-function mutations may only produce a mutant phenotype when both copies of the gene are mutated. Gantz and Bier developed a method they call mutagenic chain reaction (MCR) that autocatalytically produces homozygous mutations. MCR uses the initial mutated allele to cause a ... |
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Opinion: Is CRISPR-based gene drive a biocontrol silver bullet or global conservation threat?Webber, BLR, S.; Edwards, O. R., Proceedings of the National Academy of Sciences of the United States of America, 112:10565-10567. 2015.
Scientists have recognized the potential for applying gene drive technologies to the control of invasive species for several years, yet debate about the application of gene drive has been primarily restricted to mosquitoes. Recent developments in clustered regularly interspaced ... |
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Safeguarding CRISPR-Cas9 gene drives in yeastDiCarlo, JEC, A.; Dietz, S. L.; Esvelt, K. M.; Church, G. M., Nature Biotechnology, 33:1250-1255. 2015.
RNA-guided gene drives capable of spreading genomic alterations made in laboratory organisms through wild populations could be used to address environmental and public health problems. However, the possibility of unintended genome editing occurring through the escape of strains ... |
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Modeling the manipulation of natural populations by the mutagenic chain reactionUnckless, RLM, P. W.; Connallon, T.; Clark, A. G., Genetics, 201:425-431. 2015.
The use of recombinant genetic technologies for population manipulation has mostly remained an abstract idea due to the lack of a suitable means to drive novel gene constructs to high frequency in populations. Recently Gantz and Bier showed that the use of CRISPR/Cas9 technology ... |
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Systematic evaluation of Drosophila CRISPR tools reveals safe and robust alternatives to autonomous gene drives in basic researchPort, FM, N.; Bullock, S. L., G3-Genes Genomes Genetics, 5:1493-1502. 2015.
The Clustered Regularly Interspaced Short Palindromic Repeat/CRISPR associated (CRISPR/Cas) technology allows rapid, site-specific genome modification in a wide variety of organisms. Proof-of-principle studies in Drosophila melanogaster have used various CRISPR/Cas tools and ... |
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Genetic Control of Mosquitoes.Alphey, L., Annual Review of Entomology, 59:205-224. 2014.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their ... |
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A synthetic sex ratio distortion system for the control of the human malaria mosquitoGalizi, RD, L. A.; Menichelli, M.; Bernardini, F.; Deredec, A.; Burt, A.; Stoddard, B. L.; Windbichler, N.; Crisanti, A., Nature Communications, 5:3977. 2014.
It has been theorized that inducing extreme reproductive sex ratios could be a method to suppress or eliminate pest populations. Limited knowledge about the genetic makeup and mode of action of naturally occurring sex distorters and the prevalence of co-evolving suppressors has ... |
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Modeling the dynamics of a non-limited and a self-limited gene drive system in structured Aedes aegypti populationsLegros, MX, C. G.; Morrison, A.; Scott, T. W.; Lloyd, A. L.; Gould, F., PLOS One, 8:e83354. 2013.
Recently there have been significant advances in research on genetic strategies to control populations of disease-vectoring insects. Some of these strategies use the gene drive properties of selfish genetic elements to spread physically linked anti-pathogen genes into local ... |
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A synthetic homing endonuclease-based gene drive system in the human malaria mosquitoWindbichler, NM, M.; Papathanos, P. A.; Thyme, S. B.; Li, H.; Ulge, U. Y.; Hovde, B. T.; Baker, D.; Monnat, R. J.; Burt, A.; Crisanti, A., Nature, 473:212-215. 2011.
Genetic methods of manipulating or eradicating disease vector populations have long been discussed as an attractive alternative to existing control measures because of their potential advantages in terms of effectiveness and species specificity(1-3). The development of ... |
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Researchers eliminate mosquito population through CRISPR gene editing technologyGoss, L, Pharmafile, 2008.
Researchers at Imperial College London have been able to wipe out a population of mosquitoes through ‘gene drive’ technology. The study, published in the journal Nature Biotechnology saw a CRISPR edited gene being used to prevent female mosquitos from being born.; ; As such ... |
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Broadening the application of evolutionarily based genetic pest managementGould, F, Evolution, 62:500-510. 2008.
Insect- and tick-vectored diseases such as malaria, dengue fever, and Lyme disease cause human suffering, and current approaches for prevention are not adequate. Invasive plants and animals such as Scotch broom, zebra mussels, and gypsy moths continue to cause environmental ... |
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Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiaeWindbichler, NP, P. A.; Crisanti, A., PLOS Genetics, 4:1-9. 2008.
We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes ... |
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Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryosWindbichler, NP, P. A.; Catteruccia, F.; Ranson, H.; Burt, A.; Crisanti, A., Nucleic Acids Research, 35:5922-5933. 2007.
Homing endonuclease genes (HEGs) are selfish genetic elements that combine the capability to selectively disrupt specific gene sequences with the ability to rapidly spread from a few individuals to an entire population through homologous recombination repair events. Because of ... |
