Gene Technique That Alters CCR5-Producing Gene Increases Resistance To HIV In Mice, Study Finds

Main Category: HIV / AIDS
Also Included In: Genetics;  Biology / Biochemistry
Article Date: 04 Jul 2008 - 7:00 PDT

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Altering the gene that produces CCR5 protein on the surface of immune cells using a harmless virus was found to significantly increase resistance to HIV in mice, according to a study published Sunday in the journal Nature Biotechnology, the Press Trust of India reports (Press Trust of India, 7/1).

The virus, called a "zinc-finger nuclease," can inhibit the production of CCR5, which is the protein on the surface of immune cells that HIV attaches to, NewScientist.com reports. The "zinc-finger" part of the molecule targets and binds exclusively to genetic material only found in the CCR5 gene. The "nuclease" of the zinc-finger is an enzyme that opens and alters the gene that produces CCR5 to inhibit production of the CCR5 protein, NewScientist.com reports. After this process, the cell is then effectively immune to HIV infection.

For the study, Philip Gregory, vice president for research at Richmond, Calif.-based Sangamo Biosciences, and colleagues infected half the mice with human T-cells treated with the zinc-finger nucleases and the other half with unaltered T-cells. All the mice were then infected with HIV. After six weeks, all of the mice showed some HIV resistance. "We saw a ten-fold suppression of the virus in the treated mice compared with controls, and we saw a five-fold increase in the number of circulating T-cells," Gregory said. He added, "What's really exciting is that the change in the genome is permanent, and inherited by all 'daughter' T-cells created when the alerted T-cells multiply" (Coghlan, NewScientist.com, 6/30).

The company plans to begin human studies of the treatment before the end of this year, Bloomberg reports (Lauerman, Bloomberg, 6/29). According to the researchers, if the treatment is successful in human trials, it could offer a more effective way for controlling HIV for people living with the virus. "The zinc-finger approach has significant potential compared to other strategies," Ed Berger, an NIH researcher credited for helping establish the link between HIV and CCR5, said. He added, "With genetic knockout of CCR5 by the zinc finger, the cells lacking CCR5 have a selective advantage." John Moore, co-discoverer of the CCR5-HIV link, said although the science is excellent, he doubts whether the gene can be inhibited in enough T-cells to make a difference to people living with the disease (NewScientist.com, 6/30).

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