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takyon writes:

CRISPR 'gone wild' has made stocks swoon, but studies show how to limit off-target editing

The fear that CRISPR-based genome repair for preventing or treating genetic diseases will be derailed by "editing gone wild" has begun to abate, scientists who are developing the technique say. Although there are still concerns that CRISPR might run amok inside patients and cause dangerous DNA changes, recent advances suggest that the risk is not as high as earlier research suggested and that clever molecular engineering can minimize it.

"Progress is being made at a pretty stunning rate," said biochemist David Liu, of Harvard University and the Broad Institute, who has developed several versions of CRISPR. A parade of new discoveries, he said, "suggests that it's possible to use these genome-editing tools and not make unintended edits."

Upgrade makes genome editor CRISPR more muscular, precise

Many groups are trying to do better, and now, a team led by chemist David Liu at Harvard University has engineered a version of CRISPR that potentially is both more dexterous and more precise.

[...] The new work, reported online in the 28 February issue of Nature, modifies the Cas9 enzyme, creating at least four times as many potential docking sites. In theory, this could allow researchers to, say, cripple or replace many parts of genes associated with human disease that CRISPR currently cannot touch.

Evolved Cas9 variants with broad PAM compatibility and high DNA specificity (DOI: 10.1038/nature26155) (DX)

Preprints:

• NmeCas9 is an intrinsically high-fidelity genome editing platform (open, DOI: 10.1101/172650) (DX)
• No unexpected CRISPR-Cas9 off-target activity revealed by trio sequencing of gene-edited mice (open, DOI: 10.1101/263129) (DX)
• In vivo CRISPR-Cas gene editing with no detectable genome-wide off-target mutations (open, DOI: 10.1101/272724) (DX)
• High-precision CRISPR-Cas9 base editors with minimized bystander and off-target mutations (open, DOI: 10.1101/273938) (DX)

Original Submission