Beyond CRISPR: A guide to the many other ways to edit a genome

Heidi Ledford in Nature:

CasThe CRISPR–Cas9 tool enables scientists to alter genomes practically at will. Hailed as dramatically easier, cheaper and more versatile than previous technologies, it has blazed through labs around the world, finding new applications in medicine and basic research. But for all the devotion, CRISPR–Cas9 has its limitations. It is excellent at going to a particular location on the genome and cutting there, says bioengineer Prashant Mali at the University of California, San Diego. “But sometimes your application of interest demands a bit more.” The zeal with which researchers jumped on a possible new gene-editing system called NgAgo earlier this year reveals an undercurrent of frustration with CRISPR–Cas9 — and a drive to find alternatives. “It’s a reminder of how fragile every new technology is,” says George Church, a geneticist at Harvard Medical School in Boston, Massachusetts. NgAgo is just one of a growing library of gene-editing tools. Some are variations on the CRISPR theme; others offer new ways to edit genomes.

CRISPR–Cas9 may one day be used to rewrite the genes responsible for genetic diseases. But the components of the system — an enzyme called Cas9 and a strand of RNA to direct the enzyme to the desired sequence — are too large to stuff into the genome of the virus most commonly used in gene therapy to shuttle foreign genetic material into human cells. A solution comes in the form of a mini-Cas9, which was plucked from the bacterium Staphylococcus aureus1. It’s small enough to squeeze into the virus used in one of the gene therapies currently on the market. Last December, two groups used the mini-me Cas9 in mice to correct the gene responsible for Duchenne muscular dystrophy.

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