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Unusually small enzymes from extra-large viruses allow the CRISPR–Cas gene-editing system to slip into cells and target a broad range of genetic sequences — a finding that could help manipulate genomes more easily than before.

The CRISPR–Cas complex used in labs worldwide originated as a bacterial immune mechanism that recognizes viral DNA and directs Cas enzymes to cut it. A variation on the standard CRISPR–Cas system is found in the ‘Biggiephages’, a class of viruses that infect bacteria. They have extra-large genomes, but their Cas enzymes are about half the size of those in other CRISPR–Cas systems.

Jennifer Doudna at the University of California, Berkeley, and her colleagues found that Cas enzymes from Biggiephages can be programmed to target a wider range of DNA sequences than can conventional Cas proteins. They can also be delivered into cells easily — a boon for CRISPR-based therapies, because getting the gene-editing machinery to where it’s needed in the body is a major challenge.

The enzymes, which can edit genes in human and plant cells, are a powerful addition to the CRISPR–Cas toolbox, the researchers say.

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