Better Genetic Fix
Precision tools for therapy

Context: For a genetic engineer, putting an entire gene into a cell is much easier than correcting a few misspellings in DNA. The relatively blunt tools of recombinant DNA are ill-suited for fine tasks like editing specific DNA sequences in living cells. Now, researchers at Sangamo BioSciences in Richmond, CA, have invented the most precise tools to date for altering DNA sequences in living cells.

Methods and Results: Michael Holmes and colleagues assembled collections of proteins known as zinc fingers. Different combinations of zinc fingers can recognize DNA sequences of up to 30 letters, which is enough to pinpoint specific spots in the genome. To change the DNA at the intended site, the researchers add an enzyme that cuts DNA and triggers a natural process that repairs breaks in DNA by copying sequences from matching strands. The last part of the DNA-changing machinery is the DNA sequence to be copied. The researchers demonstrated their technique by inserting the DNA-binding machines into human white blood cells that had mutations that cause severe combined immune deficiency. The machines fixed the mutations in nearly a fifth of the cells, a phenomenal success rate.