A theory of resistance to multiplexed gene drive demonstrates the significant role of weakly deleterious natural genetic variation.

ABSTRACT: Evolution of resistance is a major barrier to successful deployment of gene-drive systems to suppress natural populations, which could greatly reduce the burden of many vector-borne diseases. Multiplexed guide RNAs (gRNAs) that require resistance mutations in all target cut sites are a promising antiresistance strategy since, in principle, resistance would only arise in unrealistically large populations. Using stochastic simulations that accurately model evolution at very large population sizes, we explore the probability of resistance due to three important mechanisms: 1) nonhomologous end-joining mutations, 2) single-nucleotide mutants arising de novo, or 3) single-nucleotide polymorphisms preexisting as standing variation. Our results explore the relative importance of these mechanisms

SUBMITTER: Khatri BS 

PROVIDER: S-EPMC9371675 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature