A novel method of “gene editing” has passed its phase I safety trial, a study including six treatment-experienced HIV positive men with abnormally low CD4+ cell counts. This therapeutic technique revolves around zinc finger nucleases, which are small proteins designed to bind and edit specific DNA sequences. Presented by Sangamo BioSciences on 28 February 2011 at the Conference on Retroviruses and Opportunistic Infections in Boston, the study described the therapeutic effect of nucleases designed to generate HIV-immune cells by disrupting function of a single gene. Researchers obtained a sample of CD4+ cells from each patient and used Sangamo’s zinc finger nuclease to disrupt the CCR5 gene, intending to prevent cellular entry. The R5 target was inspired by the small population of people with a natural chemokine mutation that provides HIV resistance. The modified cells were then returned to the original donor yielding positive results—five of the six men showed increases in CD4 counts after receiving the treatment. It is suggested that repeat treatment could establish a high percentage of resistant cells and stall disease progression.
With no serious side effects observed, the nuclease technique is a promising venue for antiviral therapy and possibly the treatment of many other diseases caused by agents other than HIV. However, the technique has a long way to go. It is currently unclear if the increases in CD4+ populations were directly due to CCR5 disruption or because the extracted cells were activated for in vitro growth. It is also unclear what percentage of a CD4+ population would need to be HIV-resistant to “liberate patients from a lifetime of antiretroviral drugs.” The technique must also be refined for higher efficiency and tested more thoroughly for off-target effects.
Ledford H. Patients Targeted gene editing enters clinic. Nature. 2011. 471(16). Online. http://www.nature.com/news/2011/110301/full/471016a.html