Findings boost HIV gene therapy optimism

A kind of gene therapy has been shown to protect monkeys against HIV infection.

The potential treatment instructs muscle cells to produce a protein that effectively neutralises the virus.

Lead researcher Professor Michael Farzan of the Scripps Research Institute in Florida, USA, told the BBC: 'We are closer than any other approach to universal protection, but we still have hurdles, primarily with safety for giving it to many, many people.'

'We're very proud of it and we think it's a big deal, but we are biased.'

Currently, the most effective treatment for HIV infection is antiretroviral therapy. These medicines are able to successfully keep the total amount of virus in the body to a minimum, but cannot eliminate it completely.

Numerous attempts have been made to create an HIV vaccine, but the diversity of strains has made both a vaccine and a cure so far unattainable.

Here, scientists took a different approach. They created a two-armed protein molecule able to block two binding sites on the surface of the HIV virus which would normally lock on to the host's cells.

After initial testing of their new molecule, called eCD4-Ig, the scientists synthesised genetic instructions for making the molecule and placed them inside a harmless carrier virus, an adeno-associated virus, or AAV. This gene therapy tool was designed so that once the AAV-modified virus infected a cell, it would cause the cell to make eCD4-Ig indefinitely.

The researchers injected the genetically modified AAV into four monkeys. Then they exposed both the treated monkeys and four untreated monkeys to an HIV-like virus six times at increasingly higher doses. None of the treated monkeys became infected, while all of the untreated monkeys did.

Crucially, eCD4-Ig was still expressed 40 weeks after the final injection, suggesting that it may provide sustainable protection.

'Our molecule appears to be the most potent and broadest inhibitor of HIV entry so far described in a preclinical study,' said Professor Farzan. 'If one could inject either eCD4-Ig or our gene therapy tool into people with an HIV infection, it might control HIV for extended periods in the absence of antiretroviral drugs.'

The scientists hope that their may work both as a preventative and as a treatment for chronically infected individuals.

However, in an accompanying opinion article HIV researcher Dr Nancy Haigwood of Oregon Health and Science University, observed that the sample size of the monkey experiments was 'quite small' and that larger animal studies were needed.

She added that future work should also test the treatment's effectiveness against traditional routes of infection -via mucus membranes, rather than via injection.

The research was published in the journal Nature.