Researchers from the University of Glasgow have solved a scientific riddle that could lead to the development of more effective gene therapies.

For years, scientists involved in gene therapy have struggled to accurately target therapeutic genes to the areas of the body requiring treatment. Often such ineffective treatments lead to serious side effects which compromises the ability to use the treatment in clinical settings.

Now Professor Andy Baker and his team have unravelled one of the remaining barriers for use of viruses for gene therapy.

The results are reported in this week’s edition of the highly respected scientific journal, Cell.

The University of Glasgow team, in collaboration with colleagues at University College London and the Medical Research Council Clinical Sciences Centre, worked with adenoviruses, a class of virus that cause respiratory, intestinal, and eye infections in humans. They were then mutated to allow them to be used in the gene therapy treatment.

The Professor of Molecular Medicine said: “Gene therapy is a technique for using genes to treat disease. One of the most common forms of this technique involves injecting genetically-modified viruses, in this case adenoviruses, into the bloodstream.”

He added: “But a huge drawback of this method is the tendency for the adenovirus to accumulate in the liver. This can lead to unwanted side effects due to expression of genes in the wrong place in the body.

“We have now identified the mechanism that the adenovirus uses to transfer genes to liver cells. We then developed new ways to block this mechanism.”

This may be highly useful in the future for treating serious diseases such as cancer and cardiovascular disease by targeting the treatment efficiently to the diseased cells.

Professor Baker, who is based at the University of Glasgow’s British Heart Foundation Cardiovascular Research Centre, said: “Scientists have been trying for years to mutate adenoviruses genetically to stop them from going to the liver. But it turns out that they have been working on the wrong protein all along.

“We targeted a different protein (the hexon protein) and found that mutating or simply blocking this eliminated gene transfer in the liver, even when large amounts of viruses were injected into the bloodstream.

“We have found the most important pathway that the virus used for liver infection and this is a real breakthrough for gene therapy research that uses this type of virus.”

Although gene therapy is in clinical development with many trials completed and ongoing, it is not yet a routine medical intervention for patients and advances are still being made into improving our understanding of how the techniques can most effectively be used.

As scientists discover more about diseases and the viruses that can be used to treat them, the more effective the therapies being developed will be.

Findings like those made by Professor Baker and his team significantly advance the understanding of gene therapies and the University of Glasgow is now working on a patent for the technique.

Funding for the research was supplied by the European Commission, the Biotechnology and Biophysical Research Council, the British Heart Foundation, the Medical Research Council and the Katharine Dormandy Trust.

Notes for editors

To find out more or to speak to Professor Andy Baker, please call Ray McHugh in the University of Glasgow Media Relations Office on 0141 330 3535 or email r.mchugh@admin.gla.ac.uk


First published: 8 February 2008

<< February