Genome editing: Enhancing CRISPR specificity to avoid breaks

A fully programmable CRISPR - Cas genome editing system that mediates the precise insertion of DNA into the genome is described in a paper published online in Nature this week. The approach avoids making double - strand breaks in the target DNA, which can lead to unintentional changes in the genetic code.

Conventional CRISPR - Cas genome editing systems employ bacterial proteins that are targeted by a guide RNA to the location in the genome of the desired change. The system works by creating double-strand breaks in the DNA, allowing new genetic information to be inserted. However, the repair system needed to heal the double - strand break is sometimes prone to making errors.

Sam Sternberg and colleagues have shown that a CRISPR - Cas system from Vibrio cholerae can facilitate the insertion of DNA without making double-strand breaks. They find that a protein encoded by the Tn7-like transposon helps to mediate direct integration of the transposon sequence into the genome of Escherichia coli using a guide RNA and the CRISPR Cascade complex. The involvement of the CRISPR system in promoting spread, or ‘jumping’, of transposons around the genome offers new insight into the transposition process. Furthermore, this system offers an alternative path to improve the specificity of CRISPR genome editing, such as might be used in gene therapies or crop engineering.

doi: 10.1038/s41586-019-1323-z

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