GENETICALLY modified bacteria that release HIV-blocking proteins might prevent people who have unprotected sex from becoming infected by the virus.
A study published this week shows that the souped-up bugs help shut out the virus from human cells in the test tube. 鈥淲e are working to try to bring this to the clinic as soon as possible,鈥� says Peter Lee of Stanford University in California.
With an effective HIV vaccine many years away and condoms not always popular, interest is growing in microbicides, vaginal medications that can protect against infection (快猫短视频, 8 February 2003, p 42). And as women control their use, such 鈥渃hemical condoms鈥� could have added value in developing countries where women have little power in relationships, and where they might be forced to have unprotected sex.
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Several potential candidates are being tried out in clinical trials. One hurdle is ensuring that chemicals that look good in the test tube do not harm the vaginal mucous membrane, making women more susceptible to infection.
Lee and his colleagues have instead used the bacterium Lactobacillus jensenii, hoping that it will do no harm because it is a natural part of vaginal flora. The researchers engineered it to secrete CD4, a protein on human cell surfaces that HIV binds to when it infects cells.
When they cultured the GM bacteria together with human cells and HIV, the bacteria secreted CD4 proteins that bound to the virus, and stopped it from entering cells (Proceedings of the National Academy of Sciences, DOI:10.1073/pnas.1934747100). Lee has founded a company called Osel, which has developed freeze-dried tablets of L. jensenii that will keep for up to a year without refrigeration.
One potential benefit of a living microbicide is that it may linger in the vagina for days or even weeks. Most of the chemical microbicides in development would have to be applied each time a couple have sex.
But only clinical trials would show if the GM bacteria work in the vagina, in the presence of mucus and semen and perhaps other sexually transmitted pathogens, warns Alan Stone, chairman of the International Working Group on Microbicides. And before such trials are carried out, Stone wants to boost the protection the bacterium offers.
It may be possible to improve protection by altering the CD4 protein that the bacterium produces and by engineering it to secrete other microbicide proteins, says Stone.
Another problem is that many people, including those in developing countries, are wary of anything that involves GM organisms. For instance, Zambia rejected food aid shipments containing GM maize earlier this year. 鈥淲e hope preventing HIV infection is a situation where the benefit-to-risk ratio is so high that it would overcome those objections,鈥� says Lee.鈥�