Sangamo is using zinc finger nuclease-mediated editing technology (ZNF) to replicate the naturally occurring human mutation in CCR5, a chemokine receptor that renders individuals largely resistant to infection with the most common strain of HIV. Sangamo’s approach comprises removal of CD4+ T-cells from the blood of immunologic non-responders HIV-infected subjects who are currently on highly active antiretroviral therapy (HAART), having undetectable levels of the virus but a suboptimal CD4+ T-cell counts. These CD4+ T-cells are then treated with Sangamo’s ZFNs that modify the DNA sequence encoding the CCR5 gene. The process indeed generates CCR5-modified, autologous T-cells (SB-728-T), which are then infused back into HIV/AIDS patients. The data obtained are actually stunning. The approach so far has proven to be safe, as infusions of SB-728-T are well tolerated. The CCR5-modified cells successfully engrafted in all subjects studied and resulted in a durable improvement in total CD4+ T-cell counts in five of six of the subjects analyzed. Five of the six subjects exhibited sustained improvements in their CD4:CD8 T-cell ratio, which is an indicator of immunologic health. The ZFN-CCR5-modified cells exhibited normal T-cell growth kinetics and trafficking and underwent selective expansion in the gut mucosa, a major reservoir of virus in the body, suggesting that the cells were resistant to HIV infection.
Nature also selected ZNF to be the method of the year for 2011: