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#2: Altered Immune Cells Block HIV

Lab-made proteins are revolutionizing AIDS therapy 
by retrofitting the immune system so it 
resists HIV. Human trials are already under way.

By Jill NeimarkJanuary 5, 2012 6:00 AM


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Talk of curing AIDS made front-page news last year, in part due to an astonishing new gene-editing technology: lab-engineered proteins called zinc finger nucleases. The finger-shaped, zinc-containing molecules, developed by California-based Sangamo BioSciences, can enter cells and snip any desired gene. Using this approach, scientists were able to excise the gene for an all-important receptor, called CCR5, located on the surface of the CD4 immune cells that HIV primarily invades. Without CCR5, the virus cannot slip inside and do its damage.

In February 2011 virologist Jay Lalezari of Quest Clinical Research reported the first use of this technology in humans. He treated nine men who had been hiv positive for 20 years or more, were on combination antiretroviral therapy, and yet had persistently low counts of the cd4 cells, signaling the continued presence of the virus. To implement therapy, he separated cd4 cells from the rest of the blood and conducted zinc finger nuclease editing in the lab to delete CCR5. Then he grew more of those cells and infused them back into the body. Of six patients Lalezari has reported on, five have seen impressive results. “Their CD4 counts went up,” he says. “The ratio of CD4 and another type of immune cell, CD8, which is often abnormally reversed in HIV, normalized. The HIV-resistant cells even migrated to the gut mucosa, an important site for the virus.”

A similar trial launched at the University of Pennsylvania has shown equal promise. In that case, six patients suspended antiretro­viral therapy for 12 weeks after infusion with zinc finger nuclease–altered CD4 cells. Without drugs to rein it in, HIV rebounded at first, but its levels subsequently dropped in all six; in one, the virus became undetectable by the end of the 12-week period, when antiretroviral treatment resumed. Future studies may involve infusion of higher numbers of altered cells. And in another advance, virologist Paula Cannon of the University of Southern California used zinc finger nucleases to create human stem cells that lack CCR5. So far she has treated mice with the engineered cells, which give rise to HIV-resistant immune cells. Human trials should follow.

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