Homing gene drives can transfer rapidly between Anopheles gambiae strains with minimal carryover of flanking sequences

Poppy Pescod, Giulia Bevivino, Amalia Anthousi, Josephine Shepherd, Ruth Shelton, Fabrizio Lombardo and Tony Nolan ()
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Poppy Pescod: Liverpool School of Tropical Medicine
Giulia Bevivino: University of Rome “la Sapienza”
Amalia Anthousi: Liverpool School of Tropical Medicine
Josephine Shepherd: Liverpool School of Tropical Medicine
Ruth Shelton: Liverpool School of Tropical Medicine
Fabrizio Lombardo: University of Rome “la Sapienza”
Tony Nolan: Liverpool School of Tropical Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract CRISPR-Cas9 homing gene drives are designed to induce a targeted double-stranded DNA break at a wild type allele (‘recipient’), which, when repaired by the host cell, is converted to the drive allele from the homologous (‘donor’) chromosome. Germline localisation of this process leads to super-Mendelian inheritance of the drive and the rapid spread of linked traits, offering a novel strategy for population control through the deliberate release of drive individuals. During the homology-based DNA repair, additional segments of the recipient chromosome may convert to match the donor, potentially impacting carrier fitness and strategy success. Using Anopheles gambiae strains with variations around the drive target site, here we assess the extent and nature of chromosomal conversion. We show both homing and meiotic drive contribute as mechanisms of inheritance bias. Additionally, over 80% of homing events resolve within 50 bp of the chromosomal break, enabling rapid gene drive transfer into locally-adapted genetic backgrounds.

Date: 2024
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DOI: 10.1038/s41467-024-51225-9

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