David Liu, the pathbreaking Harvard chemist, says it’s useful to think of CRISPR — the celebrated DNA editing tool — like a pair of scissors. It can search for, bind to, and cut specific DNA sequences.
That’s an enormously useful capability, he says. But it has its limits. Cutting a mutated gene — the kind that can cause genetic disease — usually disrupts it. Disruption, though, is expected to help patients in only some cases.
“Most of the time,” Liu says, “we actually need to fix the gene,” restoring it to its normal function.
More useful than a pair of scissors, then, is a pencil — a way to edit DNA, not just cut it. That’s where Liu’s team at the Broad Institute in Cambridge comes in.
A few years ago, using an enzyme created in the lab, the team developed “base editors” capable of correcting some of the most common kinds of mutations that cause disease; since then it’s developed more sophisticated “prime editors" — essentially moving from a pencil to a word processor.
Liu, who has founded or co-founded seven companies, cautions that correcting the mutation that causes a disease is not the same as curing it. Still, he says, it’s a good start.
“Even to benefit one patient who otherwise would have had a grim prognosis . . . would be incredibly satisfying,” he says. “But the almost unbelievably exciting prospect here is, because these agents are programmable, we might be able to ameliorate dozens, or hundreds, or thousands of diseases.”