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Published February 2016 | Supplemental Material
Journal Article Open

Cas9-triggered chain ablation of cas9 as a gene drive brake

Abstract

With the advent of clustered, regularly interspaced, short palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) technology, researchers can construct gene drives that can bias the inheritance of edited alleles to alter entire populations. As demonstrated with the mutagenic chain reaction in Drosophila4, the CRISPR-Cas9 system can propagate genomic modification together with the genome-editing machinery itself. Although gene drives might have the potential to control insect-borne diseases and agricultural pests, substantial concerns have been raised over unanticipated ecological consequences as a result of drive use. Here we report the development of a potential Cas9-based gene drive 'brake' that remains inert in a wild-type genome but is activated by Cas9 to both cleave the genomic cas9 sequence and to convert an incoming cas9 allele into a brake. This means that the propagation of the brake is favored in a cas9-carrying population.

Additional Information

© 2016 Nature Publishing Group. Published online 05 February 2016. We thank D. Luginbuhl for generating transgenic flies, F. Port for providing gRNA flies, and J. Luo, T. Mosca, X. Wang, J. Li and J. Lui for advice and critical comments. This study was supported by an NIH grant (R01-DC005982) to L.L. X.J.G. was supported by an Enlight Foundation Interdisciplinary Fellowship. L.L. is an HHMI investigator. These authors contributed equally to this work: Bing Wu & Xiaojing J Gao. Accession codes. GenBank: The plasmid sequence of CATCHA has been deposited under accession number KU212289. The sequencing results of eight NHEJ alleles have been deposited under accession numbers KU212290, KU212291, KU221292, KU221293, KU221294, KU221295, KU221296 and KU212297. The authors declare no competing financial interests.

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