Daisy-chain gene drives for the alteration of local populations

Abstract

If they are able to spread in wild populations, CRISPR-based gene-drive elements would provide new ways to address ecological problems by altering the traits of wild organisms, but the potential for uncontrolled spread tremendously complicates ethical development and use. Here, we detail a self-exhausting form of CRISPR-based drive system comprising genetic elements arranged in a daisy chain such that each drives the next. “Daisy-drive” systems can locally duplicate any effect achievable by using an equivalent self-propagating drive system, but their capacity to spread is limited by the successive loss of nondriving elements from one end of the chain. Releasing daisy-drive organisms constituting a small fraction of the local wild population can drive a useful genetic element nearly to local fixation for a wide range of fitness parameters without self-propagating spread. We additionally report numerous highly active guide RNA sequences sharing minimal homology that may enable evolutionarily stable daisy drive as well as self-propagating CRISPR-based gene drive. Especially when combined with threshold dependence, daisy drives could simplify decision-making and promote ethical use by enabling local communities to decide whether, when, and how to alter local ecosystems.

Evolutionary simulations ofZ-linked suppression gene drives

“…This could limit the usefulness of W-shredders to control species like Lepidoptera and birds, where one may wish to eradicate only invasive or agriculturally damaging populations, while leaving other populations untouched. Modifications to gene drive design-such as the self-limiting 'daisy drive' system-might someday address this important concern [21,22].…”

Progress towards engineering gene drives for population control

“…Split homing endonuclease drives (also referred to as daisy drives when arranged in a chain consisting of several components; Noble et al, 2019) separate the homing endonuclease and gRNA components of a homing endonuclease drive into separate lines, rendering the cleavage and homing inactive until the lines are genetically crossed. These drives are more geographically confinable than standard homing endonuclease drives, and therefore have been recommended as a safer alternative for initial field release (Akbari et al, 2015;Esvelt et al, 2014;Noble et al, 2019). While initially demonstrated in yeast (DiCarlo et al, 2015), split homing endonuclease drives in D. melanogaster were recently developed that had comparable gene conversion efficiencies to a standard homing endonuclease drive (Champer et al, 2019;Kandul et al, 2019 preprint).…”

Alternative Techniques and Options for Risk Reduction of Gene Drives

“…For GDO-species that are determined to be released into the environment, safety strategies become more challenging because it is intended that gene drives spread within a population by mating of GDOs with their wild conspecifics. Meanwhile a number of approaches to limit the spread of GDOs in time and space have been proposed (Esvelt et al 2014;Noble et al 2019). Within the following section potential options are presented.…”