1. Diverse virus-encoded CRISPR-Cas systems include streamlined genome editors.
- Author
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Al-Shayeb B, Skopintsev P, Soczek KM, Stahl EC, Li Z, Groover E, Smock D, Eggers AR, Pausch P, Cress BF, Huang CJ, Staskawicz B, Savage DF, Jacobsen SE, Banfield JF, and Doudna JA
- Subjects
- Animals, Humans, Cryoelectron Microscopy, Gene Editing, Genome, DNA, RNA, Mammals genetics, CRISPR-Cas Systems, Bacteriophages genetics
- Abstract
CRISPR-Cas systems are host-encoded pathways that protect microbes from viral infection using an adaptive RNA-guided mechanism. Using genome-resolved metagenomics, we find that CRISPR systems are also encoded in diverse bacteriophages, where they occur as divergent and hypercompact anti-viral systems. Bacteriophage-encoded CRISPR systems belong to all six known CRISPR-Cas types, though some lack crucial components, suggesting alternate functional roles or host complementation. We describe multiple new Cas9-like proteins and 44 families related to type V CRISPR-Cas systems, including the Casλ RNA-guided nuclease family. Among the most divergent of the new enzymes identified, Casλ recognizes double-stranded DNA using a uniquely structured CRISPR RNA (crRNA). The Casλ-RNA-DNA structure determined by cryoelectron microscopy reveals a compact bilobed architecture capable of inducing genome editing in mammalian, Arabidopsis, and hexaploid wheat cells. These findings reveal a new source of CRISPR-Cas enzymes in phages and highlight their value as genome editors in plant and human cells., Competing Interests: Declaration of interests The Regents of the University of California have filed patents related to this work on which the authors are inventors. J.A.D. is a co-founder of Caribou Biosciences, Editas Medicine, Scribe Therapeutics, Intellia Therapeutics, and Mammoth Biosciences. J.A.D. is a scientific advisory board member of Vertex, Caribou Biosciences, Intellia Therapeutics, Scribe Therapeutics, Mammoth Biosciences, Algen Biotechnologies, Felix Biosciences, The Column Group, and Inari Agriculture. J.A.D. is Chief Science Advisor to Sixth Street, a Director at Johnson & Johnson, and Altos and Tempus, and has research projects sponsored by Apple Tree Partners and Roche. J.F.B. is a co-founder of Metagenomi. S.E.J. is a scientific co-founder of Inari Agriculture, and a science advisory board member to Invaio Sciences, Senda Biosciences, FL70, and Sixth Street., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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