A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias.
Sebald A N Verkuijl, Estela Gonzalez, Ming Li, Joshua X D Ang, Nikolay P Kandul, Michelle A E Anderson, Omar S Akbari, Michael B Bonsall, Luke Alphey
Nature communications · 2022-Nov-21 · PMID 36414618 · DOI 10.1038/s41467-022-34739-yAbstract
CRISPR/Cas gene drives can bias transgene inheritance through different mechanisms. Homing drives are designed to replace a wild-type allele with a copy of a drive element on the homologous chromosome. In Aedes aegypti, the sex-determining locus is closely linked to the white gene, which was previously used as a target for a homing drive element (w GDe ). Here, through an analysis using this linkage we show that in males inheritance bias of w GDe did not occur by homing, rather through increased propagation of the donor drive element. We test the same w GDe drive element with transgenes expressing Cas9 with germline regulatory elements sds3, bgcn, and nup50. We only find inheritance bias through homing, even with the identical nup50-Cas9 transgene. We propose that DNA repair outcomes may be more context dependent than anticipated and that other previously reported homing drives may, in fact, bias their inheritance through other mechanisms.
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- Conflict statement
- O.S.A. is a founder of Agragene, Inc., and has an equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. All other authors declare no competing interests.