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Measuring the impact of genetic heterogeneity and chromosomal inversions on the efficacy of CRISPR-Cas9 gene drives in different strains of Anopheles gambiae

Pescod, Poppy, Bevivino, Giulia, Anthousi, Amalia, Shelton, Ruth, Margiotta, Molly, Shepherd, Josie, Lombardo, Fabrizio and Nolan, Tony ORCID: https://orcid.org/0000-0002-2982-8333 (2023) 'Measuring the impact of genetic heterogeneity and chromosomal inversions on the efficacy of CRISPR-Cas9 gene drives in different strains of Anopheles gambiae'. The CRISPR Journal, Vol 6, Issue 5, pp. 419-429.

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Abstract

The human malaria vector Anopheles gambiae is becoming increasingly resistant to insecticides, spurring the development of genetic control strategies. CRISPR-Cas9 gene drives can modify a population by creating double-stranded breaks at highly specific targets, triggering copying of the gene drive into the cut site (‘homing’), ensuring its inheritance. The DNA repair mechanism responsible requires homology between the donor and recipient chromosomes, presenting challenges for the invasion of lab-developed gene drives into wild populations of target species An. gambiae species complex, which show high levels of genome variation.
Two gene drives (vas2-5958 and zpg-7280) were introduced into three An. gambiae strains collected across Africa with 5.3-6.6% variation around the target sites, and the effect of this variation on homing was measured. Gene drive homing across different karyotypes of the 2La chromosomal inversion was also assessed. No decrease in gene drive homing was seen despite target site heterology, demonstrating the applicability of gene drives to wild populations.

Item Type: Article
Subjects: QU Biochemistry > Genetics > QU 470 Genetic structures
QU Biochemistry > Genetics > QU 475 Genetic processes
QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1089/crispr.2023.0029
Depositing User: Maria Grimes
Date Deposited: 04 Jul 2023 15:30
Last Modified: 23 Oct 2023 09:06
URI: https://archive.lstmed.ac.uk/id/eprint/22730

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