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Daisy-chain gene drives for the alteration of local populations

By Charleston Noble, John Min, Jason Olejarz, Joanna Buchthal, Alejandro Chavez, Andrea L Smidler, Erika A DeBenedictis, George M Church, Martin A Nowak, Kevin M Esvelt

Posted 07 Jun 2016
bioRxiv DOI: 10.1101/057307 (published DOI: 10.1073/pnas.1716358116)

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.

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