January 8, 2018
There is a great deal of interest in exploring the potential of gene therapy to cure HIV. This area of research has received encouragement from recent successes in the cancer field -- the FDA has just approved the first two gene therapies for hard-to-treat malignancies.
Multiple different gene therapy strategies for HIV are under investigation. A leading approach involves genetically modifying immune system cells to resist HIV infection, with the aim of preventing the virus from being able to cause disease even if the latent reservoir is not reduced or eliminated.
Sangamo Biosciences has conducted studies involving extracting CD4 T cells from HIV-positive individuals, genetically altering them in the laboratory so that they can no longer display the HIV co-receptor CCR5, and then re-infusing them in large numbers. Some evidence of enhanced control of HIV viral load after ART interruption has been reported, but it appears that further work is needed to increase the number of gene-modified cells.
The company Calimmune is testing a dual gene therapy that inhibits both CCR5 expression and HIV fusion with target cells. In an ongoing trial, CD4 T cells and stem cells are being extracted, genetically modified, and then re-infused.
At least seven clinical trials (including several conducted by the defeatHIV collaboratory) are testing genetic modification of stem cells for HIV-positive people who need stem cell transplants to treat cancers. The hope is to use gene therapy to generate an HIV-resistant immune system, akin to what was achieved in Timothy Ray Brown using stem cells from a donor homozygous for the CCR5Δ32 mutation.
Plans are also afoot to test a type of gene therapy known as a chimeric antigen receptor (CAR) T cell against HIV -- this involves equipping immune system cells with receptors that allow them to better recognize and kill HIV-infected targets. The recently FDA-approved gene therapies for cancers comprise CAR T cells engineered to recognize malignant cells.
While trials are likely further down the road, there is excitement about the possibility of using a new gene-editing technique called CRISPR/Cas9 to try and specifically excise HIV DNA from latently infected cells. The approach has shown promise in the laboratory, but it is not yet known if it can be successfully delivered into the body.
For additional information on gene therapy research, see the interview with Paula Cannon.
[Note from TheBodyPRO.com: This article was originally published by Positively Aware in Dec., 2017. We have cross-posted it with their permission.]
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