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Cas9-mediated maternal effect and derived resistance alleles in a gene-drive strain of the African malaria vector mosquito, Anopheles gambiae. | LitMetric

AI Article Synopsis

  • CRISPR/Cas9 technologies are being used to create gene-drive systems to alter mosquito populations, aiming to reduce the spread of diseases like malaria.
  • A current problem with these gene-drive systems is the emergence of drive-resistant alleles due to unintended genetic changes (indels) from the Cas9 process, potentially disrupting the effectiveness of the gene drives.
  • Research shows that these resistant alleles are primarily generated during the early development of embryos, influenced by the presence of Cas9 and guide RNAs from gene-drive mothers.

Article Abstract

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 ability to produce drive-resistant alleles resulting from insertions and deletions (indels) caused principally by nonhomologous end-joining following chromosome cleavage. Rapid increases in the frequency of such alleles may impair gene-drive dynamics. We explored the generation of indels in the germline and somatic cells in female gene-drive lineages using a series of selective crosses between a gene-drive line, AgNosCd-1, and wild-type mosquitoes. We find that potential drive-resistant mutant alleles are generated largely during embryonic development, most likely caused by deposition of the Cas9 endonuclease and guide RNAs in oocytes and resulting embryos by homozygous and hemizygous gene-drive mothers.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157122PMC
http://dx.doi.org/10.1093/genetics/iyac055DOI Listing

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