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