This “major advance in the field” is the largest clinical trial ever to test genetically altered cells in humans, say UCLA researcher Ronald T. Mitsuyasu, MD, and colleagues.
“This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product,” the researchers report in the Feb. 15 advance online issue of Nature Medicine.
The treatment calls for patients to get shots of a growth factor that stimulates growth of white blood cells. Then the cells are taken from their blood. Blood stem cells are separated out and put in cell culture dishes.
In the culture, the patients’ own blood stem cells are infected with OZ1, a genetically engineered mouse virus that gives them an anti-HIV gene. This gene encodes an RNA molecule called a ribozyme, which specifically targets and inactivates HIV genes.
Once equipped with the anti-HIV gene, the blood stem cells are transfused back into the patient. The idea is for these stem cells to home in to the bone marrow and populate it with HIV-resistant T cells. As the older T cells die off or are killed by HIV, more and more of the body’s T cells should be HIV resistant.
Now that researchers have shown this kind of gene therapy can work, future treatments will increase the dose, improve homing to the bone marrow, and carry an even more powerful anti-HIV gene. And in the future, patients would be treated before starting anti-HIV drugs.
This gene therapy boosting or altering of blood cells could also be effective in treating cancer.
He said: “Gene therapy has the potential of needing only a one-time or infrequent administration of product and would allow the patients to control their own HIV internally without the need for continuous drug therapy.
“While this treatment is far from being perfected, it is not yet as effective or as complete as current antiretroviral therapy in controlling HIV, the study did show proof of concept that inserting and administering a single anti-HIV gene in the patients’ own blood stem cells and giving it back to them could reduce viral replication to some degree when anti-HIV medications are stopped.”
However, Professor Mitsuyasu said long-term follow up was needed to ensure the therapy was safe.
Keith Alcorn, of the HIV information service NAM, said: “The viral load responses in this study were very modest, and for any other sort of product would not justify going forward.
“However, the researchers have shown enough of an effect for us to be hopeful that a gene therapy approach to HIV treatment might eventually deliver effective treatments for the disease.”
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