Although HIV can nowadays be successfully managed with a cocktail of antiretroviral drugs that inhibit replication, the virus remains latent in the genome of infected individuals waiting to come out full throttle whenever it is given the chance. Therefore the hunt is still on for a strategy to give HIV infected cells the final blow.
In the current fast en furious era of genome editing it almost seems like every month another application is found for these tools. In fact, a team of researchers lead by Huanzhang Zhu used the on target DNA cleaving potential of zinc finger nucleases to cleave the HIV-1 provirus out of infected human T-cells.
To do this they targeted zinc finger-FokI fusions to a sequence within the extremely well conserved long terminal repeat (LTR) U3 region of the HIV-1 provirus.
Here is what they noticed:
- Conservation analysis of the zinc finger binding motif revealed a sequence similarity of 0.922, indicating a great potential in targeting all known HIV variants
- Three days after delivery of the zinc finger nuclease they showed successful cleaving of the HIV-1 provirus and a excision frequency up to 30%
- No side effects were seen on cell proliferation and cell cycle progression of uninfected cells
The team concluded that the use of their designed zinc finger as part of a therapeutic strategy, could indeed eradicate the remaining latent virus. However, they also stress that delivery of these gene-editing tools in clinical settings remains a pickle, but propose a strategy of transplanted autologous CD34+ cells pretreated with zinc-finger nuclease as the way to go.
Check out the cutting edge details in Mol. Biol. Rep. July 2014