Live-in bugs fight HIV:
Women visiting health centres in Africa could one day be offered a bacterial gel to help fight the spread of AIDS. © UNAIDS
Some of the 'friendly bacteria' found in yoghurt have been genetically modified to release a drug that blocks HIV infection.
Although the bacteria have only been tested in a lab dish, scientists are optimistic that the technique could provide a cheaper and more effective way of delivering drugs to fight the spread of AIDS, by getting the bugs to live right where the drugs are needed most. The bacterium (Lactococcus lactis) the researchers have modified naturally produces lactic acid, and so is used to produce cheese and yoghurt.
It is also found in some parts of the human anatomy, including the gut and the vagina, where the acid it produces damps down the growth of other, harmful bacteria. Some 'probiotic' yoghurts are loaded with such beasties with the aim of keeping consumers' guts healthy (see 'Gut Reaction').
Bharat Ramratnam, an HIV specialist at Brown Medical School, Providence, Rhode Island, and his colleagues have now altered the genetic make-up of L. lactis so that it generates cyanovirin, a drug that has prevented HIV infection in monkeys and human cells, and is on track for human trials in 2007. Cyanovirin binds to sugar molecules attached to the HIV virus, blocking a receptor that HIV uses to infect cells. "It's basically passive immunization," says Sean Hanniffy, a molecular biologist at the Institute of Food Research, Norwich, UK, and part of the team.Gels containing cyanovirin could afford some protection for women against the transmission of HIV, but since the drug breaks down quickly these would have to be smeared in the vagina immediately before sex.
"In some countries there's a reluctance to use these gels frequently," explains Hanniffy. Because lactic-acid bacteria live naturally in the vagina, one application of a bacterial goop should see the modified bugs thrive there for at least a week, says Hanniffy. "The next step might be to use other bacteria that can survive for even longer," he adds.
Cheap and easy
Hanniffy says that the bugs may offer advantages over injected vaccines, which often have trouble reaching peripheral areas of the body, such as mucosal surfaces in the vagina. "You need less of the therapeutic chemical if you deliver it locally," adds Lothar Steidler, a molecular biologist at Cork University in Ireland who has also worked on modifying bacteria to deliver drugs."There's also an economic issue," says Hanniffy. Simply brewing a vat of the bacteria should be much simpler and cheaper than producing a drug gel, he says.
And if the bugs could be taken orally, as in probiotic yoghurts, production should be even easier. "You could produce the drug wherever you have the facilities to make a dairy product," says Steidler. "It makes lifelong treatment more feasible from an economic point of view.""The biggest problem at the moment is treating people in developing countries," says Steidler. "This new therapeutic approach could be a profound answer to those needs."
Fear of bugs
Public fear of genetic modification may stop this research going forward, warns Hanniffy. "It's definitely a barrier right now," he says. "But if there was a success story I think we'd see a rise in acceptance."One such success might come from the first clinical trial of a transgenic bacteria, which was completed last year in the Netherlands and used altered L. lactis to deliver a drug to 10 patients with Crohn's disease, a chronic bowel disorder (see 'Better living through microbes').
This was the first time permission was given to use live genetically modified bacteria in a clinical situation, Hanniffy says. "It's a small trial, but a big step." The bugs were carefully engineered to ensure that they could not survive outside the body, and that there was no gene transfer to their host1,2.The same technique could also be used to deliver a wide variety of drugs, says Steidler.
"This technique could be a completely new kind of pharmacology," he says.The team publishes its research in the Journal of Acquired Immune Deficiency Syndrome3. They are now planning to test their HIV-fighting L. lactis in macaque monkeys.
Steidler L., et al. Science, 289 . 1352 - 1355 (2000). Article PubMed ISI ChemPort
Steidler L., et al. Nature Biotechnol., 21. 1785 - 1789 (2003).
Pusch O., et al. J. Acquir. Immune Defic. Syndr., 40 . 512 - 520 (2005).