AIDSmeds reports that Sangamo BioSciences has begun new clinical studies of its promising gene therapy SB-728-T, a potential “functional cure” for HIV infection, according to a January 9 announcement by the company. SB-728-T is a zinc finger DNA-binding protein transcription factor (ZFP TF). It disrupts the gene responsible for making CCR5 co-receptors on the surface of CD4 cells, to which HIV bonds. When CD4 cells can’t produce functional co-receptors, it is much harder for HIV to infect them. The aim of SB-728-T therapy is to grow a new population of CD4 cells that are resistant to HIV infection, and thus make antiretroviral (ARV) therapy unnecessary. The rationale for using SB-728-T comes from the case of Timothy Brown, an HIV-positive man with leukemia who received two stem cell transplants from a donor who inherited two mutated CCR5 genes (CCR5 delta32), from his father and mother, and was genetically unable to produce CD4 cells that carry functional CCR5 co-receptors. Such individuals rarely become infected with HIV. And in cases where only one mutated CCR5 gene is inherited, HIV infection can occur, but the disease tends to progress slowly. In Brown’s case, not only did the stem cell therapy cure his cancer, but it also appears to have cured his HIV infection. All efforts to locate HIV in the man’s body have been unsuccessful.
Sangamo is hoping that treating a person’s own stem cells with SB-728-T and then reinfusing them will, over time, replace HIV-susceptible cells with HIV-resistant CD4s and reduce the need for continuous antiretroviral therapy.
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