Scientists at a California-based therapeutics company have developed a mechanism to edit genes directly inside the human body that could prove safer than other known gene-editing techniques. Though CRISPR-Cas9 caught the public imagination as a powerful gene-editing technique, many researchers have cautioned that it could also induce unwanted DNA changes, including significant deletions and rearrangements near its target site in a gene, that may remain undetected until they have manifest effects. UK-based scientists had, earlier this year, pointed out deletions of several thousand nucleotides bear the site of CRISPR editing target as well as errors such as distant sequences coming together. Against such a backdrop, the California scientists’ therapy is welcome news.
The researchers at Sangamo Therapeutics, as per a report in Nature, designed enzymes that correct a specific genetic error that causes Hunter syndrome. Those afflicted are unable to digest certain complex sugars, which, upon accumulation, can damage vital organs such as the lungs, heart and brain. The Sangamo scientists used a virus to deliver gene-editing enzymes known as zinc finger nucleases—which have hitherto only been used in ex vivo gene-editing—to correct the error that switches off the enzyme iduronate-2-sulfatase (IDS). The viral shuttle carried DNA coding for the nuclease to the liver cells where IDS is generally produced. Of the four patients who received the Sangamo therapy, two showed a fall in the levels of sugars that IDS breaks down while the remaining two didn’t show any change in levels; none reported any negative fallout of the therapy. Even though many in the scientific community don’t see Sangamo’s therapy as “true” gene-editing since it involves enzyme rewriting a sequence rather than introducing a new one, many have hailed it as being of vital significance for the treatment of a broad range of diseases. More importantly, this could perhaps be the answer to problems highlighted with CRISPR.