Abstract
Gene drives are selfish genetic elements that are transmitted to progeny at super-Mendelian (>50%) frequencies. Recently developed CRISPR–Cas9-based gene-drive systems are highly efficient in laboratory settings, offering the potential to reduce the prevalence of vector-borne diseases, crop pests and non-native invasive species. However, concerns have been raised regarding the potential unintended impacts of gene-drive systems. This Review summarizes the phenomenal progress in this field, focusing on optimal design features for full-drive elements (drives with linked Cas9 and guide RNA components) that either suppress target mosquito populations or modify them to prevent pathogen transmission, allelic drives for updating genetic elements, mitigating strategies including trans-complementing split-drives and genetic neutralizing elements, and the adaptation of drive technology to other organisms. These scientific advances, combined with ethical and social considerations, will facilitate the transparent and responsible advancement of these technologies towards field implementation.
Highlights
The full introduction of a specific allele from one genetic background into another results in all progeny carrying the allele in question
Low-threshold drives can be seeded at very low numbers to do so. This Review focuses on the latter low-threshold gene drives in insects as they arguably hold the greatest promise for impacting disease transmission on continental scales and because optimized second-generation drives have been developed over the past 5 years
◀ Fig. 2 | suppression drives and mathematical modelling. a | Genetic map of one of the first CRISPR-based suppression drives inserted into the female-sterile nudel locus in Anopheles gambiae. b | Multigenerational cage studies with the nudel-drive resulted in an initial increase followed by a progressive loss of the gene-drive element without crashing the target population
Summary
Abstract | Gene drives are selfish genetic elements that are transmitted to progeny at superMendelian (>50%) frequencies. Concerns have been raised regarding the potential unintended impacts of gene-drive systems This Review summarizes the phenomenal progress in this field, focusing on optimal design features for full-drive elements (drives with linked Cas[9] and guide RNA components) that either suppress target mosquito populations or modify them to prevent pathogen transmission, allelic drives for updating genetic elements, mitigating strategies including trans-complementing split-drives and genetic neutralizing elements, and the adaptation of drive technology to other organisms. Exploiting genetic systems that link desired traits to chromosomes or genetic elements with a positive transmission bias (that is, >50%) dates back to the potential uses of chromosomal translocations by Serebrovski[1], which was further generalized and articulated by Curtis in the 1960s for spreading a desired trait throughout a target population[2] These so-called gene-drive systems or selfish genes[3] are abundant in nature. The bipartite nature and flexible programmability of CRISPR led to the rapid development of a variety of genedrive systems (Fig. 1b–f) in insects[45,46,47,48,49], mammals[50], yeast[51] and bacteria[52], several of which are discussed in this Review
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