Cell 2015-10-22

Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system.

Bernd Zetsche, Jonathan S Gootenberg, Omar O Abudayyeh, Ian M Slaymaker, Kira S Makarova, Patrick Essletzbichler, Sara E Volz, Julia Joung, John van der Oost, Aviv Regev, Eugene V Koonin, Feng Zhang

Index: Cell , doi:10.1016/j.cell.2015.09.038, (2015)

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Abstract

The microbial adaptive immune system CRISPR mediates defense against foreign genetic elements through two classes of RNA-guided nuclease effectors. Class 1 effectors utilize multi-protein complexes, whereas class 2 effectors rely on single-component effector proteins such as the well-characterized Cas9. Here, we report characterization of Cpf1, a putative class 2 CRISPR effector. We demonstrate that Cpf1 mediates robust DNA interference with features distinct from Cas9. Cpf1 is a single RNA-guided endonuclease lacking tracrRNA, and it utilizes a T-rich protospacer-adjacent motif. Moreover, Cpf1 cleaves DNA via a staggered DNA double-stranded break. Out of 16 Cpf1-family proteins, we identified two candidate enzymes from Acidaminococcus and Lachnospiraceae, with efficient genome-editing activity in human cells. Identifying this mechanism of interference broadens our understanding of CRISPR-Cas systems and advances their genome editing applications. Copyright © 2015 Elsevier Inc. All rights reserved.