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Sangamo BioSciences Announces Nature Biotechnology Study Demonstrating the Use of Zinc Finger Nucleases to Generate HIV Resistant T Cells
Date:6/30/2008

n drugs, concerning the risk of liver toxicity and the possibility of heart attacks.

Sangamo's ZFN technology represents a means of potentially circumventing these limitations or risks by specifically modifying only CD4 T-cells, the principal target of HIV pathology, in a one-time exposure of the cells to ZFNs. This results in permanent modification of the CCR5 protein such that HIV cannot enter and infect the cells. This approach 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 HIV itself. Sangamo expects to initiate a clinical trial to evaluate this approach by the end of the year.

Data Reported in the Nature Biotechnology Paper

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 by the permanent genetic modification of the CCR5 gene. 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 (virus that uses the CCR5 co-receptor to enter cells), resulting in enrichment of ZFN- generated CCR5-disrupted cells in the population upon long-term exposure to virus (>50 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 hi
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SOURCE Sangamo BioSciences, Inc.
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