CRISPR 2.0

You’ve probably heard of the molecular scalpel CRISPR-Cas9, which can edit or delete whole genes. Now, scientists have developed a more precise version of the DNA-editing tool that can repair even smaller segments of a person’s genome.

In two studies published this month, one in Nature and another in Science, researchers from the Broad Institute of MIT and Harvard describe a new way to edit DNA and RNA, called base editing. The approach could one day treat a range of inherited diseases, some of which currently have no treatment options.

The human genome contains six billion DNA letters, or chemical bases known as A, C, G and T. These letters pair off—A with T and C with G—to form DNA’s double helix. Base editing, which uses a modified version of CRISPR, is able to change a single one of these letters at a time without making breaks to DNA’s structure.

That’s useful because sometimes just one base pair in a long strand of DNA gets swapped, deleted, or inserted—a phenomenon called a point mutation. Point mutations make up 32,000 of the 50,000 changes in the human genome known to be associated with diseases.

In the Nature study, researchers led by David Liu, a Harvard chemistry professor and member of the Broad Institute, were able to change an A into a G. Such a change would address about half the 32,000 known point mutations that cause disease.

To do it, they modified CRISPR so that it would target just a single base. The editing tool was able to rearrange the atoms in an A so that it instead resembled a G, tricking cells into fixing the other DNA strand to complete the switch. As a result, an A-T base pair became a G-C one. The technique essentially rewrites errors in the genetic code instead of cutting and replacing whole chunks of DNA.

Liu said base editing isn’t meant to be a replacement to traditional gene editing with CRISPR, but rather another option for altering the genome in an attempt to correct disease. If CRISPR is akin to a pair of scissors, base editing is more like a pencil, he said.

Previously, researchers had created base editors capable of making the opposite kind of swap—changing a G into an A. Substitutions of a G for an A in certain parts of the DNA represent about 15 percent of disease-associated point mutations.