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

cer. "Most importantly, we have demonstrated that a single treatment with our CCR5-specific ZFNs generates a population of HIV-resistant T-cells similar to the situation in individuals carrying the natural CCR5-delta32 mutation. We have shown that these ZFN-modified cells are made permanently resistant to HIV. Furthermore, the cells selectively survive and expand in an animal after HIV infection providing a reservoir of healthy and uninfectable immune cells. In a patient, such cells could be available to fight both opportunistic infections and HIV itself. In addition, we have reported on the successful ZFN-modification of clinical-scale quantities of human CD4 T-cells. The modified cells exhibited the expected properties of normal CD4 T-cells minus a functional CCR5 receptor. This demonstrates that ZFN-modified human CD4 T-cells can be produced in the quantities required for the translation of this program into the clinic which is our immediate goal for this ZFP Therapeutic."

Several major pharmaceutical companies have initiated programs to develop small molecule or antibody approaches to block the binding of HIV to CCR5. However, a small molecule or antibody approach requires the constant presence of a sufficiently high concentration of drug to block therapeutically relevant numbers of the CCR5 protein, which is present in thousands of copies on the surface of each T-cell and other tissues in the body. One such drug was recently approved by the US Food and Drug Administration with a "black box" warning, the strongest for prescription 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 so that HIV cannot enter and infect the cells. This appro
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SOURCE Sangamo BioSciences, Inc.
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