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Performance analysis of novel toxin-antidote CRISPR gene drive systems.
Champer, Jackson; Kim, Isabel K; Champer, Samuel E; Clark, Andrew G; Messer, Philipp W.
Afiliación
  • Champer J; Department of Computational Biology, Cornell University, Ithaca, NY, 14853, USA. jc3248@cornell.edu.
  • Kim IK; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853, USA. jc3248@cornell.edu.
  • Champer SE; Department of Computational Biology, Cornell University, Ithaca, NY, 14853, USA.
  • Clark AG; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853, USA.
  • Messer PW; Department of Computational Biology, Cornell University, Ithaca, NY, 14853, USA.
BMC Biol ; 18(1): 27, 2020 03 12.
Article en En | MEDLINE | ID: mdl-32164660
ABSTRACT

BACKGROUND:

CRISPR gene drive systems allow the rapid spread of a genetic construct throughout a population. Such systems promise novel strategies for the management of vector-borne diseases and invasive species by suppressing a target population or modifying it with a desired trait. However, current homing-type drives have two potential shortcomings. First, they can be thwarted by the rapid evolution of resistance. Second, they lack any mechanism for confinement to a specific target population. In this study, we conduct a comprehensive performance assessment of several new types of CRISPR-based gene drive systems employing toxin-antidote (TA) principles, which should be less prone to resistance and allow for the confinement of drives to a target population due to invasion frequency thresholds.

RESULTS:

The underlying principle of the proposed CRISPR toxin-antidote gene drives is to disrupt an essential target gene while also providing rescue by a recoded version of the target as part of the drive allele. Thus, drive alleles tend to remain viable, while wild-type targets are disrupted and often rendered nonviable, thereby increasing the relative frequency of the drive allele. Using individual-based simulations, we show that Toxin-Antidote Recessive Embryo (TARE) drives targeting an haplosufficient but essential gene (lethal when both copies are disrupted) can enable the design of robust, regionally confined population modification strategies with high flexibility in choosing promoters and targets. Toxin-Antidote Dominant Embryo (TADE) drives require a haplolethal target gene and a germline-restricted promoter, but they could permit faster regional population modification and even regionally confined population suppression. Toxin-Antidote Dominant Sperm (TADS) drives can be used for population modification or suppression. These drives are expected to spread rapidly and could employ a variety of promoters, but unlike TARE and TADE, they would not be regionally confined and also require highly specific target genes.

CONCLUSIONS:

Overall, our results suggest that CRISPR-based TA gene drives provide promising candidates for flexible ecological engineering strategies in a variety of organisms.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Antitoxinas / Sistemas CRISPR-Cas / Tecnología de Genética Dirigida / Antídotos Idioma: En Revista: BMC Biol Asunto de la revista: BIOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Antitoxinas / Sistemas CRISPR-Cas / Tecnología de Genética Dirigida / Antídotos Idioma: En Revista: BMC Biol Asunto de la revista: BIOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos