DNA Scissors: The Future of Human Gene Therapy?

Traditionally, gene therapy has been something of a hit and miss affair. Sadly more miss than hit. Whilst the science is elegant, what happens in practise rarely lives up to expectations.

So let's look at how to cure a hypothetical patient who has a genetic disorder caused by a single defective gene that you would like to replace. The patient is infected with a virus containing a good copy of the gene. Taking advantage of the virus's molecular machinery the good gene is inserted into your target cell. But once you've sent the little biological package on its way into the patient's body, it's a matter of crossing your fingers in the hope that it lands in the right spot, and works well without triggering cancer. Trying to slip a gene into a precise spot, without causing internal mayhem, is a tricky job.

In the past few years gene therapy has been used successfully to treat children with X-SCID (severe combined immunodeficiency disease), but there were gene therapy cons. Three children went on to develop leukaemia, possibly because the retrovirus carrying the good gene settled near an oncogene.

The odds of gene therapy success could soon be about to increase with the adoption of a relatively new technology involving an exotic bunch of proteins called zinc finger nucleases. They were discovered and initially developed by Sir Aaron Klub in the UK's Medical Research Council's Laboratory of Molecular Biology in Cambridge.

The clever thing about these proteins is that they attach or bind to specific places on chromosomes. Working just like a pair of scissors, (hence the nickname 'DNA Scissors') they cut the DNA at specific locations; say where your bad gene is, allowing it to be repaired by the cell's own repair machinery.

Up until now, if researchers wanted to get their hands on zinc finger nucleases they had to pay a biotech company $25,000 for a set. But what's given the field a shot in the arm is that an eight lab consortium led by molecular biologist J. Keith Joung at Massachusetts General Hospital in Boston has developed 66 of their own pools of zinc fingers. The Zinc Finger Consortium will make the pools available at a fraction of the cost, approximately $200.

So far the technology has worked on fruit flies, plants, worms and human cells in a laboratory setting. It's still too early for a therapeutic treatment, but with more researchers soon to be working in the field, it's perhaps the best chance of tackling genetic diseases since the first rush of excitement about gene therapy. The technology could allow the benefits of gene therapy to be realised.