Advertisement covers The 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2012)

Zinc Finger Gene Therapy Continues to Show Promise

November/December 2012

For HIV-positive individuals on HAART with low CD4 T-cell counts (immune nonresponders), there are limited therapeutic options. CCR5 is one of the major co-receptors on CD4 cells which HIV uses to enter. Zinc finger nuclease (ZFN) technology modifies the CCR5 gene on CD4 T-cells from the patient's own body in an effort to increase them while creating cells that are resistant to HIV. The "byproduct" of this process is called SB-728-T.

Data presented from a small phase 1 study suggest that this approach to HIV therapy offers the hope of providing a persistent source of CD4 T-cells that are resistant to HIV infection.

The technique, developed by Sangamo Biosciences, uses a process called apheresis to collect T-cells from the patient's blood. The ZFN is then used to interfere with CCR5 gene expression, and the altered SB-728 T-cells multiply and are infused back into the individual.

SB-728-T was safe and well tolerated with minor reversible infusion-related symptoms, and resulted in significant increases in CD4 T-cells averaging 233 cells/mm3 at 14 days, and 93 cells/mm3 at 12 months. The authors concluded that the preliminary data suggest that SB-728-T provides "sustained improvement in the CD4 compartment and has the potential to reconstitute the immune system." Phase 1 and 2 studies are moving forward.

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