The gentle touch

时间:2019-03-07 05:14:00166网络整理admin

By Nell Boyce in Washington DC A MORE subtle approach to gene therapy could provide a permanent cure for some genetic diseases. The first human trials, on children in the Amish religious community suffering from a rare syndrome called Crigler-Najjar, may begin next year. Conventional gene therapy relies on modified viruses to get healthy genes into cells. But the genes are inserted randomly into the genome, which may disrupt other genes. It also means that the activity of the introduced genes is unlikely to be regulated in the same way as it would be in a normal, healthy cell. Given these problems, some researchers have been trying to repair damaged genes rather than adding healthy ones. The best they had managed was to correct 1 per cent of cells cultured in a Petri dish (New Scientist, 11 April 1998, p 7). Now Clifford Steer and his colleagues at the University of Minnesota Medical School in Minneapolis have achieved much better results in rats, using a technique that exploits the body’s own DNA repair mechanisms. The rats were missing a single nucleotide in the gene for a liver enzyme that breaks down bilirubin, a toxic waste product created when the body destroys old red blood cells. Steer and his colleagues injected them with microscopic fat globules containing “chimeric” molecules made of DNA and RNA. These were designed to bind to the target DNA in such a way that DNA repair enzymes would make the change that fixes the fault. The same technique has been used to genetically engineer plants (New Scientist, 31 July, p 4). A single injection into the rats’ tails led to a significant decrease in bilirubin levels that seemed to be permanent. In the latest Proceedings of the National Academy of Sciences (vol 96, p 10 349), Steer reports that the genetic defect was fixed in up to 20 per cent of the rats’ liver cells. “This is the first time anyone has been able to go in and correct a gene defect in an animal,” he says. A similar genetic defect causes Crigler-Najjar, which is unusually prevalent in the Amish of Lancaster County, Pennsylvania. Children who have the syndrome are required to sleep under special blue lights that destroy bilirubin—a practice tolerated by the Amish despite their reputation for shunning technology. If this fails they may need a liver transplant. Steer hopes that if his gene-repair technique works in people as it does in rats, it may be possible to cure Crigler-Najjar. Other gene therapists are excited by Steer’s rat results—particularly since conventional gene therapy doesn’t usually alter such a high proportion of the target cells. Mark Kay of Stanford University in California admits he was sceptical about results that Steer published last year. “But I don’t think there’s any doubt any more.” The limitation of the technique is that it can only change or add one nucleotide at a time. “Sickle cell and cystic fibrosis are two very good examples of where this would be useful,