3 people with drug-resistant HIV become first to undergo a new form of gene therapy

3 people with drug-resistant strains of HIV have become the first to undergo a new form of gene therapy designed to block the virus.

The idea is to use a modified form of HIV to deliver an "antisense" gene to the immune cells that HIV infects. This is integrated into the cells' genome, and stays there until a cell is infected. Then it is switched on, and produces RNA complementary to the "sense" RNA encoding a viral protein. In theory, the RNAs should bind together, blocking viral replication.

Lab tests by the Maryland-based company VIRxSYS showed viral replication is at least 100 times lower in treated cells. So in July last year the company started treating patients by filtering immune cells from their blood, exposing the cells to very low doses of the modified virus, and then putting them back into the body.

Like existing antiretroviral drugs, the approach will not completely eliminate HIV from the body. But because the antisense RNA fragment is very long, HIV should never be able to mutate enough to become resistant to it, Boro Dropulic, chief scientific officer of VIRxSYS, told the RNAi 2004 meeting in Boston last week.

It is the first time that this has been attempted with modified HIV, and Dropulic says the results so far are encouraging. But Richard Sutton of Baylor College of Medicine in Houston is sceptical, saying the many problems inherent in gene therapy for HIV have led others to give up on the approach. "A lot of people, including large pharma, have seen the writing on the wall," he says.

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