TY - JOUR T1 - Daisy-chain gene drives for the alteration of local populations JF - bioRxiv DO - 10.1101/057307 SP - 057307 AU - Charleston Noble AU - John Min AU - Jason Olejarz AU - Joanna Buchthal AU - Alejandro Chavez AU - Andrea L. Smidler AU - Erika A. DeBenedictis AU - George M. Church AU - Martin A. Nowak AU - Kevin M. Esvelt Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/06/06/057307.abstract N2 - RNA-guided gene drive elements could address many ecological problems by altering the traits of wild organisms, but the likelihood of global spread tremendously complicates ethical development and use. Here we detail a localized form of CRISPR-based gene drive composed of genetic elements arranged in a daisy-chain such that each element drives the next. “Daisy drive” systems can duplicate any effect achievable using an equivalent global drive system, but their capacity to spread is limited by the successive loss of non-driving elements from the base of the chain. Releasing daisy drive organisms constituting a small fraction of the local wild population can drive a useful genetic element to local fixation for a wide range of fitness parameters without resulting in global spread. We additionally report numerous highly active guide RNA sequences sharing minimal homology that may enable evolutionary stable daisy drive as well as global CRISPR-based gene drive. Daisy drives could simplify decision-making and promote ethical use by enabling local communities to decide whether, when, and how to alter local ecosystems.Author’s Summary ‘Global’ gene drive systems based on CRISPR are likely to spread to every population of the target species, hampering safe and ethical use. ‘Daisy drive’ systems offer a way to alter the traits of only local populations in a temporary manner. Because they can exactly duplicate the activity of any global CRISPR-based drive at a local level, daisy drives may enable safe field trials and empower local communities to make decisions concerning their own shared environments.For more details and an animation intended for a general audience, see the summary at Sculpting Evolution. ER -