Gene targeting raises cure hopes

12.00.00am UTC (GMT +0000) Wed 19th Mar 2008

A more efficient way to shut down rogue genes raises hopes of new therapies for conditions like diabetes and HIV. Systematically knocking out single genes potentially gives scientists unprecedented control over the processes which cause disease.

US and UK researchers have developed synthetic proteins which can target individual genes quickly, simply and with a high degree of success. The study appears in Proceedings of the National Academy of Sciences.

The new technique is already being used in trials on a range of diseases.

The regulation of gene expression is controlled by regulatory proteins called transcription factors. The researchers have created their own synthetic versions of these transcription factors called zinc-finger nucleases.

They can be used to cut into and inactivate a target gene in a very precise way, without affecting other nearby genes. It is also possible to use a similar approach to activate beneficial genes by introducing new DNA at the point where the gene is cut.

Zinc-finger proteins were discovered and developed by Sir Aaron Klug, based at the Medical Research Council's Laboratory of Molecular Biology in Cambridge. His work has been taken on by US firm Sangamo Bio Sciences.

The targetting of individual genes is currently carried out using a process known as homologous recombination, which involves the exchange of genetic material between the target gene and DNA created in the lab. However, this process is time consuming, can be very elaborate, requiring the insertion of markers into the target gene, and is not always very efficient.

Sir Aaron said: "The beauty of zinc-finger nucleases lies in their simplicity. Where other methods are long, arduous and often messy, it is relatively easy to switch off genes using this method. The zinc-finger design allows us to target a single gene, while the nuclease disrupts the gene. The single step process is extremely quick and reliable and opens up exciting possibilities for research and gene therapy."

Animal trials are already under way to use the technique to knock out the receptor of HIV in immune system T-cells of patients with Aids. If successful this will render the T-cells immune from HIV infection, and enable them to fight disease. Clinical trials to aid patients with blocked blood vessels are also under way.

Dr Vincent Cunliffe, a genetics expert from the University of Sheffield, described the technique as "a powerful method for efficiently and selectively inactivating" individual genes. He said: "This technology will have many applications in future research."