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"VIVO" Method Limits CRISPR-Cas9 Off-Target Mutations

Accepted submission by takyon at 2018-09-13 13:32:32

New Technique Limits CRISPR-Cas9 Off-Target Mutations: A mouse study details a method called VIVO that predicts the accuracy of any guide RNA. []

One of the barriers to using CRISPR-Cas9 gene editing in the clinic is the possibility that the enzyme will clip DNA in the wrong spot. In a study published in Nature [] [DOI: 10.1038/s41586-018-0500-9] [DX []] today (September 12), researchers describe a strategy to predict these off-target mutations throughout the genome and show in mice that a carefully designed guide RNA strand does not produce any detectable slip-ups.

The study confirms that "you'd better make sure that you've got a really accurate guide RNA," says Janet Rossant [], a developmental biologist at the University of Toronto and the Hospital for Sick Children who did not participate in the work. "This [method] is a better way of testing for how specific that guide RNA will be before you go into animal models and, of course, into humans," she adds.

According to coauthor Marcello Maresca [], a biologist at AstraZeneca in Sweden, one long-term goal of his company is to be able to use therapeutic gene editing to address a number of human diseases. "However, realizing the potential of CRISPR medicines requires the development of methods to enable the efficient modification of the target gene with no effects elsewhere in the genome," he writes in an email to The Scientist.

VIVO = "verification of in vivo off-targets".

Related: CRISPR Safer than Thought; Misleading Study Found Shared Mutations in Closely Related Mice []
CRISPR Becomes More Precise []
Paper That Found CRISPR "Off-Target Effects" Retracted []
Repair of Double-Strand Breaks Induced by CRISPR Leads to Large Deletions and Complex Rearrangements []
Did CRISPR Really Fix a Genetic Mutation in These Human Embryos? []

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