RNA-guided DNA insertion with CRISPR-associated transposases.

Strecker, Jonathan; Ladha, Alim; Gardner, Zachary; Schmid-Burgk, Jonathan L; Makarova, Kira S; Koonin, Eugene V; Zhang, Feng · Science · 2019

basic_science · Level V

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Abstract

CRISPR-Cas nucleases are powerful tools for manipulating nucleic acids; however, targeted insertion of DNA remains a challenge, as it requires host cell repair machinery. Here we characterize a CRISPR-associated transposase from cyanobacteria <i>Scytonema hofmanni</i> (ShCAST) that consists of Tn7-like transposase subunits and the type V-K CRISPR effector (Cas12k). ShCAST catalyzes RNA-guided DNA transposition by unidirectionally inserting segments of DNA 60 to 66 base pairs downstream of the protospacer. ShCAST integrates DNA into targeted sites in the <i>Escherichia coli</i> genome with frequencies of up to 80% without positive selection. This work expands our understanding of the functional diversity of CRISPR-Cas systems and establishes a paradigm for precision DNA insertion.

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