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

Pescod, Poppy, Bevivino, Giulia, Anthousi, Amalia, Shepherd, Josie, Shelton, Ruth, Lombardo, Fabrizio and Nolan, Tony ORCID: https://orcid.org/0000-0002-2982-8333 (2024) 'Homing gene drives can transfer rapidly between Anopheles gambiae strains with minimal carryover of flanking sequences'. Nature Communications, Vol 15, Issue 1, e6846.

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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.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 460 Genomics. Proteomics QU Biochemistry > Genetics > QU 500 Genetic phenomena QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1038/s41467-024-51225-9
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	04 Sep 2024 15:37
Last Modified:	04 Sep 2024 15:37
URI:	https://archive.lstmed.ac.uk/id/eprint/25127

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