Researchers lay plans to test ambitious therapy.
Scientists have unveiled plans to test an HIV treatment based on a much-touted technique that hasn't yet been tried on people.
The treatment is based on a mechanism called RNA interference (RNAi), which can be used by cells to shut down invading viruses. Scientists and the biotechnology industry believe the interference pathway is a tremendously promising target for a variety of therapies. Two clinical trials of RNAi therapies have already begun, but the HIV proposal goes a step further, combining RNAi with gene therapy. It will be a closely watched test of whether the field can fulfil its potential.
Leaders of the trial described their plans to the US Recombinant DNA Advisory Committee (RAC) on 21 September. The committee gave generally favourable reviews, but recommended further safety tests before the study begins.
One of the trial's leaders is John Rossi, a molecular biologist at City of Hope's Beckman Research Institute in Duarte, California. Rossi says his team will perform these extra tests before asking the Food and Drug Administration (FDA) for approval to begin the trial.
If the FDA says yes, Rossi and his team will test the therapy on five HIV patients who have a blood cancer called lymphoma. They will treat the patients' lymphoma with aggressive chemotherapy and a bone-marrow transplant — a normal procedure. But before the transplant, they will use gene therapy to add stretches of DNA to stem cells in the bone marrow. It is hoped that molecules encoded by the added genes will trigger the cells' RNAi defences against HIV.
The trial is different from the RNAi trials already under way, because the molecules used in those studies remain in the body for only a short time. The City of Hope researchers will deliver DNA packaged into a gene-therapy vector that could persist in patients for months or even years.
The RAC is cautious for that reason, and because the trial will set another precedent: it is the first in which researchers will use a lentivirus to deliver therapeutic genes to patients' stem cells. Lentiviruses are related to retroviruses, which were used in gene-therapy trials that caused cancer in three children with a rare immunodeficiency disease (see Nature 433, 561; 200510.1038/433561a).
“We need to be careful, because now we have a study that's using a vector in the same family as the retrovirus, it's going into stem cells, and it's going into immunodeficient patients,” says Diane Wara, who chairs the RAC.
The City of Hope team will monitor its patients to see whether the therapy causes cancerous mutations. The preliminary experiments are promising, Wara told Nature, emphasizing that she was speaking for herself, and not for the RAC. “John Rossi's work is beautifully done, and his data are very compelling.”
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Check, E. Pioneering HIV treatment would use interference and gene therapy. Nature 437, 601 (2005). https://doi.org/10.1038/437601b
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DOI: https://doi.org/10.1038/437601b