Sangamo BioSciences said a study has been published that demonstrates in mice the efficacy of a human stem cell therapy for HIV based on its proprietary zinc finger DNA-binding protein nuclease technology or ZFN. In essence, the technology is used to edit the CCR5 gene to mimic the effects of a naturally-occurring variant that renders some people resistant to HIV infection. By disrupting the CCR5 gene, exploited as a doorway by HIV into the infection fighting cells of the immune system, it holds the promise of rendering infected patients resistant to the disease.

The work, which was carried out by researchers at the Keck School of Medicine of the University of Southern California, in collaboration with Sangamo scientists, was published as an Advance Online Publication in Nature Biotechnology. The study in mice showed that a one-time exposure to CCR5-specific ZFNs resulted in the generation of an HIV-resistant population of human hematopoietic stem cells–the stem cells that give rise to the various types of cells that make up the immune system.

The study also showed these cells engrafted in mice lacking a normal immune system so they do not reject human cells. After 8-12 weeks the engrafted ZFN-modified human cells could be identified as different immune cell types in the peripheral blood and various tissues of the mouse, suggesting that they were functionally normal. The study suggests that human HSCs can be modified with ZFNs, expand and differentiate and have a selective advantage in the presence of HIV allowing them to evade infection and destruction leaving them able fight opportunistic infections and HIV itself.

The study followed news last year that an American with HIV who was able to end his regimen of HIV drugs after being treated for leukemia with a bone marrow transplant of stem cells from a donor that had a naturally occurring CCR5 mutation that made him resistant to HIV.

“These are very exciting data that provide proof of concept for a new approach to HIV treatment,” says John Zaia, Chair in Gene Therapy and Chair of Virology at City of Hope. He said the paucity of human donors with this natural CCR5 mutation and the risks of bone marrow transplants require “a more practical solution to make this a therapeutic option.” He says modifying human stem cells using zinc fingers to recreate CCR5 mutation “is a potential solution.”

Zaia is the leader of the recent $14.5 million Disease Team Research Award granted by the California Institute for Regenerative Medicine to a multidisciplinary team of investigators which includes City of Hope, researchers at USC, and Sangamo scientists. The award funds the preclinical development of a ZFN CCR5-targeted approach which aims to complete an application to the U.S. Food and Drug Administration to begin clinical testing of this ZFN method.