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CRISPR–CAS9 gene-editing complex from Streptococcus pyogenes.

The Cas9 enzyme (red, artist’s impression) snips DNA (orange). Improved versions of Cas9 promise to expand the usefulness of the CRISPR–Cas9 genome-editing technique. Credit: Alamy

CRISPR-Cas9 genome editing

All-purpose enzymes boost CRISPR’s powers

The gene-editing system could target a broad swathe of the genome with the help of versatile enzymes.

Newly developed enzymes allow the CRISPR–Cas9 genome-editing system to target a huge range of mutations in human cells — an advance that could lead to the development of CRISPR-based treatments for human disease.

Conventional CRISPR complexes include an enzyme called Cas9, which recognizes and cuts a target stretch of DNA. To edit DNA sequences, the Cas9 enzyme must detect a short genetic sequence, called a protospacer-adjacent motif (PAM), embedded in the target DNA. The most commonly used Cas9 variant doesn’t work properly unless it detects a PAM that has a chemical makeup known as NGG.

Benjamin Kleinstiver at Harvard Medical School in Boston, Massachusetts, and his colleagues engineered Cas9 enzymes that can recognize a wide variety of PAMs, not just the NGG sequence. The authors used their new enzymes to edit the genomes of human cells in a laboratory dish, targeting many previously inaccessible regions of the genome. The updated system could correct mutations associated with conditions such as heart disease, type 2 diabetes, osteoporosis and chronic pain.

The approach could make the vast majority of the human genome editable, the researchers say.

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