Homing-based gene drives can introgress rapidly into local genetic backgrounds with minimal chromosomal conversion in Anopheles gambiae

Tony Nolan, Poppy Pescod, Giulia Bevivino et al.,  Research Square,  2023.

CRISPR-Cas9 gene drive control strategies use a homing selfish genetic element which induces a double-stranded break at the target site and is copied into the opposing chromosome, breaking an essential gene and ensuring super-Mendelian inheritance. During the copying process SNPs could potentially be transferred from one chromosome to another, converting tracts of the target to match the recipient. This would reduce the ability of gene drives to escape their genetic background of origin, with potential impacts on carrier fitness and the success of the strategy. In this study we use Anopheles gambiae strains with variation around the target site to determine the extent of chromosomal conversion during gene drive activity and the mechanism of inheritance bias. We confirm a homing-based mechanism and show that two thirds of homing events are resolved within 50 bp, showing that gene drive introgression into a wild strain can occur within one generation.

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