Concepedia

A toxin-antidote CRISPR gene drive system for regional population modification

Jackson Champer, Esther Lee, Emily Yang, Chen Liu, Andrew G. Clark, Philipp W. Messer

Nature Communications · 2020 · 152 citations · 53 references

Open access

TL;DR

Engineered homing gene drives can rapidly spread genetic changes but are hindered by resistance and high invasiveness. The study introduces the Toxin‑Antidote Recessive Embryo (TARE) drive. The TARE drive disrupts a target gene to create recessive lethal alleles while rescuing carriers with a recoded version of the target. Modeling and cage experiments show that the TARE drive spreads only above a threshold frequency, achieves 88‑95% transmission, and can propagate through a population in six generations without resistance, indicating its potential for regionally confined population modification.

Abstract

Engineered gene drives based on a homing mechanism could rapidly spread genetic alterations through a population. However, such drives face a major obstacle in the form of resistance against the drive. In addition, they are expected to be highly invasive. Here, we introduce the Toxin-Antidote Recessive Embryo (TARE) drive. It functions by disrupting a target gene, forming recessive lethal alleles, while rescuing drive-carrying individuals with a recoded version of the target. Modeling shows that such drives will have threshold-dependent invasion dynamics, spreading only when introduced above a fitness-dependent frequency. We demonstrate a TARE drive in Drosophila with 88-95% transmission by female heterozygotes. This drive was able to spread through a large cage population in just six generations following introduction at 24% frequency without any apparent evolution of resistance. Our results suggest that TARE drives constitute promising candidates for the development of effective, flexible, and regionally confinable drives for population modification.