Suicidal Gene Therapy Fights Hepatitis C

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April, 21 2003 7:23

An international collaboration of scientists has demonstrated the promise of gene therapy for combating hepatitis C infections, which affect about 200 million people worldwide. Currently, the protein alpha interferon is the only approved therapeutic for treating hepatitis C infection and in many cases it shows only limited effectiveness. Reporting in the May issue of Nature Biotechnology, scientists demonstrate that adenoviral gene therapy can lead to significant reductions in levels of hepatitis C virus in mice containing virally infected human liver cells.

As hepatitis C lurks within human liver cells, the authors designed their strategy to specifically induce death in those cells harboring the virus, with the hope that this would prevent production of new infectious virus. To accomplish their goal, they turned to a cellular protein called the BID precursor (BH3-interacting domain death agonist precursor), which triggers the killing of cells only when degraded by enzymes called proteases. Because BID precursor is not normally degraded in healthy cells or cells infected with hepatitis C virus, the researchers engineer into BID precursor a recognition site for a protease found in hepatitis C virus. In this way, they hoped that hepatitis C–infected cells exposed to the modified BID molecules would be specifically targeted and killed.

Sure enough, when the authors used adenoviruses to deliver the gene for the modified BID precursor into human liver cells implanted in mice, they found that BID was cleaved only in those cells infected by the hepatitis C virus and expressing the viral protease. In infected cells, BID went on to cause cell death, effectively halting progression of hepatitis infection. In the majority of cases, BID gene therapy resulted in substantial decreases in the quantity of virus; in mild infections, the clearance of virus was complete. The authors’ approach holds promise as a therapeutic option for hepatitis C as well as for other types of viral infections.

Author contact:
Christopher D. Richardson
Ontario Cancer Institute, Toronto, Ontario, Canada
Tel: +1 416 204 2280; E-mail: chrisr@uhnres.utoronto.ca

Also available online.

Author: Trevor M. D'Souza

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