A gene therapy technique that repairs faulty genes by 'editing' their DNA could lead to new treatments for inherited blood disorders and HIV (human immunodeficiency virus), say US researchers. The approach could help address safety concerns over current gene therapy methods, many of which rely on specially adapted viruses to deliver working genes to cells. The team, lead by researchers at Sangamo Biosciences in Richmond, California, published their results in the early online edition of Nature.
The scientists tested the technique on human immune cells growing in the laboratory, which had the genetic defect that causes severe combined immune deficiency (SCID). Children affected by SCID have a faulty gene that means their immune systems do not work properly, so their bodies cannot effectively fight infections. To repair the gene, the team put together a protein that could 'home in' on the section of DNA code that contained the fault. They then fused this protein to an enzyme that would snip the DNA at that specific point, and simultaneously inserted a new piece of correct DNA code into the cell - effectively carrying out a biological 'find and replace' process. The replacement DNA is incorporated into the gene via a naturally-occurring repair mechanism, called recombination.
The gene editing technique successfully corrected the faulty SCID gene in 18 per cent of the immune cells. The scientists now hope to use the approach on blood stem cells taken from SCID patients, to develop a new type of gene therapy for this disorder. As well as SCID, the technique could also be used to treat other hereditary blood diseases, such as sickle cell anaemia and thalassaemia. Edward Lanphier, president of Sangamo said: 'We can target any gene we want, go into human cells and correct mistakes'. The team also hopes to tackle HIV, by altering genes that make the proteins through which HIV gets into immune cells.
Previous SCID gene therapy treatment using viruses to deliver working genes has proved effective, but three children in a French trial for X-linked SCID developed leukaemia - one of whom has died. The cancer is thought to have been triggered by the insertion of the virus's genetic material into that of the immune cell, thereby switching on a cancer-causing gene. The new technique should avoid this problem, but there other potential concerns, cautions US geneticist John Wilson. It could be difficult to make the technology specific enough, and, as he points out, 'we don't want to be cutting up the genome willy-nilly'.
Sue Mayer, of the pressure group GeneWatch UK, called for the new gene editing approach to be regulated so that it would not be used for 'trivial' reasons. 'We sometimes overstate how many people would want to use it for that, but unless there are safeguards in place then the temptation will always be there', she told the Guardian newspaper. Lanphier said that the technique could potentially target genes not involved in disease, but added that he thought the reality is that 'people who apply it will do so for medical reasons'.