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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.

Why It Matters: Experimental therapies for cancer, transplant rejection, and immune disorders remove blood cells or stem cells, alter their DNA, and infuse them back into the patient. In the past, such techniques have caused fatal side effects because researchers could not uniformly control where those genetic alterations took place. The Sangamo technique avoids this risk by pinpointing exactly where a new DNA sequence will go. It could also effectively erase a gene. Sangamo hopes to turn off a gene for a protein on white blood cells that HIV uses to enter cells. But the benefits go beyond possible therapies: the Sangamo technique promises to become a standard precision tool for biotechnology.

Source: Urnov, F. D., et al. 2005. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature (in press).

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Tagged: Biomedicine

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