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Sangamo BioSciences demonstrates its ZFP treatment protects cells from HIV infection

Sangamo BioSciences, Inc. today announced that data from its program to develop a ZFP Therapeutic for HIV/AIDS were presented at the 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, DC. The study represents the first demonstration that cells can be made resistant to HIV infection by treatment with Sangamo's proprietary zinc finger DNA-binding protein nucleases (ZFNTM) designed to specifically disrupt the CCR5 gene.

In its anti-HIV preclinical research program, Sangamo has designed ZFNs that can be used to disrupt the CCR5 gene, a receptor required for HIV entry into immune cells. The researchers found that ZFN-modified cells were resistant to HIV infection whereas control cells were infected when challenged with the virus. Furthermore, when CCR5 expression was experimentally restored in the ZFN-modified cells, HIV was once again able to infect these cells. Sangamo has shown disruption of the CCR5 gene in a number of different cell types including T-cells, the target cell for this therapeutic approach.

"CCR5 is an important target in the fight against HIV/AIDS," stated Edward Lanphier, Sangamo's president and CEO. "Individuals with a natural mutation of their CCR5 gene have been shown to be resistant to HIV infection. Several major pharmaceutical companies have initiated programs to develop small molecule drugs to block HIV binding to CCR5, but in recent months two trials have been halted, one due to reports of liver toxicity of the candidate drug. We believe that using ZFNs to permanently modify the CCR5 gene specifically in T-cells and thus directly block the expression of the protein on the surface of these cells may have several advantages over the systemic effects of other drugs in development."

Small molecule or antibody approaches require the constant presence of antagonist in high enough concentrations to block therapeutically relevant numbers of the CCR5 protein, of which there are approximately 10,000 copies on the surface of each T-cell. In contrast, brief exposure of T-cells to Sangamo's ZFNs has been shown to result in permanent modification of the CCR5 gene and consequent alteration of the CCR5 protein.

"We believe that the data presented at ICAAC provide another important validation of our novel approach to HIV," said Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "By administering ZFNs to patients, we could potentially provide HIV-infected individuals with a reservoir of healthy and uninfectable T-cells that would be available to fight both opportunistic infections and HIV itself. In this program, we have been working in close collaboration with Dr. Carl June at the University of Pennsylvania with the goal of initiating a Phase 1 clinical trial to test our ZFP Therapeutic in 2006."

Dr. Carl June, Director of Translational Research at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine, is a leader in the field of research testing T-cell therapies for cancer and HIV infection. Dr. June stated, "After the recent negative news regarding trials with pharmacologic blockade of CCR5, it is very important that we focus on positive results involving this well-validated disease target. I am encouraged by Sangamo's findings and look forward to collaborating with the Company further to bring this promising approach into the clinic."


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Source:jjackson@burnsmc.com


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