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      Gene-drive suppression of mosquito populations in large cages as a bridge between lab and field


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          CRISPR-based gene-drives targeting the gene doublesex in the malaria vector Anopheles gambiae effectively suppressed the reproductive capability of mosquito populations reared in small laboratory cages. To bridge the gap between laboratory and the field, this gene-drive technology must be challenged with vector ecology.

          Here we report the suppressive activity of the gene-drive in age-structured An. gambiae populations in large indoor cages that permit complex feeding and reproductive behaviours.

          The gene-drive element spreads rapidly through the populations, fully supresses the population within one year and without selecting for resistance to the gene drive. Approximate Bayesian computation allowed retrospective inference of life-history parameters from the large cages and a more accurate prediction of gene-drive behaviour under more ecologically-relevant settings.

          Generating data to bridge laboratory and field studies for invasive technologies is challenging. Our study represents a paradigm for the stepwise and sound development of vector control tools based on gene-drive.


          Experimental analysis of gene drive population dynamics has mostly been limited to small cage trials. Here the authors, to fill the gap between lab based studies and field studies, use large indoor cages and see population suppression without the emergence of resistant alleles

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          Most cited references33

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          Multiplex genome engineering using CRISPR/Cas systems.

          Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.
            • Record: found
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            CRISPResso2 provides accurate and rapid genome editing sequence analysis

              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes

              Complete population collapse of malaria vector Anopheles gambiae in cages is achieved using a gene drive that targets doublesex. Supplementary information The online version of this article (doi:10.1038/nbt.4245) contains supplementary material, which is available to authorized users.

                Author and article information

                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                28 July 2021
                28 July 2021
                : 12
                : 4589
                [1 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Department of Life Sciences, , Imperial College London, ; London, UK
                [2 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, , Johns Hopkins University, ; Baltimore, MD USA
                [3 ]GRID grid.511365.5, Genetics & Ecology Platform, , Polo d’Innovazione di Genomica Genetica e Biologia, ; Terni, Italy
                [4 ]National Research Council Research Institute on Terrestrial Ecosystems, Terni, Porano Italy
                [5 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Department of Zoology, , University of Oxford, ; Oxford, UK
                [6 ]GRID grid.48004.38, ISNI 0000 0004 1936 9764, Department of Vector Biology, , Liverpool School of Tropical Medicine, ; Liverpool, UK
                [7 ]GRID grid.7839.5, ISNI 0000 0004 1936 9721, Institute of Occupational, Social and Environmental Medicine, , Goethe University, ; Frankfurt am Main, Germany
                [8 ]GRID grid.11505.30, ISNI 0000 0001 2153 5088, Department of Biomedical Sciences, , Institute of Tropical Medicine Antwerp, ; Antwerp, Belgium
                Author information
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                : 11 April 2021
                : 5 July 2021
                Funded by: FundRef https://doi.org/10.13039/100000865, Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation);
                Award ID: Target Malaria
                Award Recipient :
                Funded by: Supported by a grant from the Bill & Melinda Gates Foundation and from the Open Philanthropy Project Fund, an advised fund of Silicon Valley Community Foundation.
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                © The Author(s) 2021

                environmental biotechnology,synthetic biology,behavioural ecology,population dynamics


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