CRISPR 2.0?

A pioneer of the gene-editing technique discovers a protein that could improve its accuracy.

By | September 28, 2015

Crystal structure of a Cas9 in complex with an RNA guide and a stretch of target DNAWIKIMEDIA, H. NISHIMASU ET AL.Searching bacteria for an alternative to Cas9, the enzyme used in the CRIPSR system to cut DNA at a site specified by RNA guides, synthetic biologist Feng Zhang of the Broad Institute in Cambridge, Massachusetts, and his colleagues discovered a protein called Cpf1 in some bacteria that use CRISPR for viral defense. Taking a closer look at Cpf1 from 16 microbial species, the research team identified two that could cut human DNA, they reported last week (September 25) in Cell.

“It’s a noteworthy addition to the biology [of CRISPR] and a valuable addition to the tool box,” North Carolina State University molecular biologist Rodolphe Barrangou, who did not participate in the research, told Science.

Important differences exist between Cpf1 and Cas9. Cas9 relies on two RNA molecules to specify the DNA to be cut, while Cpf1 only requires one, for instance. And the nature of the cut is also different: Cas9 cuts both DNA strands at the same location, while Cpf1 snips DNA such that there are short, single-stranded pieces on either side of the cut. “The sticky ends carry information that can direct the insertion of the DNA,” Zhang told Nature. “It makes the insertion much more controllable.”

The sticky ends could also improve the efficiency of CRISPR gene editing, as the blunt ends left by Cas9 cuts are often simply stuck back together, rather than incorporating new DNA. “Boosting the efficiency would be a big step for plant science,” Iowa State University plant biologist Bing Yang, who was not involved in the study, told Nature. “Right now, it is a major challenge.”

The new discovery could also hold financial value, as the Broad and the University of California, Berkeley, continue to duke it out over who first invented CRISPR editing tools such as Cas9. While the US Patent and Trademark Office considers intervening in the case, Cpf1 could sidestep the problem altogether. “The greatest value may be more in terms of the patent landscape than a scientific advancement,” the University of Minnesota’s Dan Voytas told MIT Technology Review.

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