Base editing with a Cpf1-cytidine deaminase fusion.

Li, Xiaosa; Wang, Ying; Liu, Yajing; Yang, Bei; Wang, Xiao; Wei, Jia; Lu, Zongyang; Zhang, Yuxi et al. · Nat Biotechnol · 2018

basic_science · Level V

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Abstract

The targeting range of CRISPR-Cas9 base editors (BEs) is limited by their G/C-rich protospacer-adjacent motif (PAM) sequences. To overcome this limitation, we developed a CRISPR-Cpf1-based BE by fusing the rat cytosine deaminase APOBEC1 to a catalytically inactive version of Lachnospiraceae bacterium Cpf1. The base editor recognizes a T-rich PAM sequence and catalyzes C-to-T conversion in human cells, while inducing low levels of indels, non-C-to-T substitutions and off-target editing.

Medical subject headings