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Sangamo BioSciences Presents Data Demonstrating 'In Vivo' Protection Against HIV Infection by CCR5-ZFN Therapeutic
Date:9/18/2007

ach could potentially enable the generation of a reservoir of protected CD4 T-cells that are available to fight the opportunistic infections that are characteristic of AIDS as well as the AIDS virus itself.

Data Reported in the ICAAC Presentation

The reported results demonstrate that a one-time exposure to CCR5-specific ZFNs resulted in the generation of an HIV-resistant population of human primary T-cells that permanently expressed disrupted CCR5 proteins. These ZFN-modified CD4 T-cells expanded stably in HIV-infected cultures for several weeks and appeared to behave identically to untreated T-cells except that they were resistant to infection by HIV. ZFN treated primary CD4 T-cells and transformed CD4 cell lines resisted infection with R5-tropic HIV, resulting in enrichment of ZFN-generated CCR5-disrupted cells in the population upon long-term exposure to virus (>70 days). Importantly, in the presence of HIV, ZFN-modified CD4 T-cells also preferentially expanded in a mouse model. The modified cells were infused into mice that lack a normal immune system and thus do not reject human cells. After 33 days, the mice were sacrificed and analyzed for the presence of ZFN-modified cells. Researchers determined that ZFN-modified cells engrafted normally in the mouse and that the proportion of modified cells present at the end of the experiment was greater than two to three fold higher in mice in the presence of HIV infection (which was statistically significant p=0.008). These data suggest that, in the presence of HIV, the ZFN-modified cells have a selective advantage and evade HIV infection and destruction.

In addition, researchers demonstrated successful ZFN-modification of clinical-scale quantities of human CD4 T-cells and that these modified cells exhibited the expected properties of normal T-cells. This demonstrates that ZFN-modified human CD4 T-cells could be produced in quantities required for the translation of this program into the clinic.


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SOURCE Sangamo BioSciences, Inc.
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