Data from Sangamo’s developmental program has shown that its zinc finger DNA-binding protein (ZFP) can be used to make cells resistant to HIV infection by permanently modifying the DNA sequence encoding CCR5, an essential co-receptor for the entry of HIV into immune cells.
“ZFN-modified cells were shown to be resistant to HIV infection. Moreover, the cells were able to grow in culture under conditions in which they were exposed to the virus for prolonged periods. When CCR5 expression was experimentally restored to the ZFN-modified cells, HIV was once again able to infect them demonstrating the selectivity of the approach,” said Dr Dale Ando, Sangamo’s vice president of therapeutic development and chief medical officer.
Several major pharmaceutical companies have initiated programs developing small molecule or antibody approaches to block the binding of HIV to CCR5. Unfortunately, these approaches require the constant presence of antagonist in high enough concentrations to block therapeutically relevant numbers of the CCR5 protein, which is present in thousands of 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.
The company intends to initiate a phase I clinical trial to test this HIV ZFP therapeutic in the second half of 2006. The present findings were presented in an oral session at the 13th Conference on Retroviruses and Opportunistic Infections (CROI) held in Denver.