© K. Eward / Science Photo LibraryZinc-finger nucleases can delete or swap genes by recognizing and cutting specific DNA sequences.
Molecular tools that alter specific sites in the genome hold huge promise for genetic research and gene therapy. But the first genome-wide surveys of where these tools, called zinc-finger nucleases, act has surprised researchers.
Two papers published today, one in
Nature Biotechnology1 and one in
Nature Methods,2 show that although zinc-finger nucleases are highly specific, the methods previously used to predict where they might go wrong miss the mark.
Zinc-finger nucleases are enzymes that can be designed to find specific DNA sequences in the genome and cut them out, deleting those sequences or swapping one gene for another. Clinical trials are underway in HIV patients of zinc-finger nucleases that remove a gene that allows the virus to enter immune cells.
The enzymes should be a vast improvement over conventional gene therapy, which uses viruses to insert genes into the genome almost at random. This unpredictability has caused problems: in one of the first clinical trials of gene therapy, five children treated for a rare immune disorder developed leukaemia because the viral vector embedded itself near cancer-causing genes.
3Zinc-finger nucleases are far more specific, but they still have the potential to make unwanted changes. "We need to know if they actually go where we think they will go," says David Segal, a molecular biologist at the University of California, Davis, who was not involved in the latest studies. "Nobody wants to have a zinc-finger nuclease loose in their cells that could make cancer-causing mutations."