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.
The new method is also called ABE (adenine base editors).
before ABE can be tried in human patients, Liu says, doctors would need to determine when to intervene in the course of a genetic disease. They would also have to figure out how to best deliver the gene editor to the relevant cells—and to prove the approach is safe and effective enough to make a difference for the patient.
The ABE gene-editing process is efficient, effectively editing the relevant spot in the genome an average of 53 percent of the time across 17 tested sites, Liu said. It caused undesired effects less than 0.1 percent of the time, he added. That success rate is comparable with what CRISPR can do when it is cutting genes.
It’s such an incredible moment to work (and invest) in life sciences.