Fingers Point Way To HIV Treatment

HIV enters T cells by recognizing two different cell-surface receptors -- a primary receptor, called CD4, and a co-receptor, such as CCR5 or CXCR4. Rare individuals who are born with mutations in the CCR5 gene lack functional CCR5 molecules on their T cells and are naturally resistant to HIV infection.

To see if this natural mechanism of viral resistance could be mimicked in normal T cells that do express functional CCR5, Carl June and colleagues deliberately disrupted the CCR5 gene using a genetic treatment. The treatment involves zinc-finger endonucleases, enzymes that cut DNA at specific sequences. By making variants of these endonucleases, researchers can control which genomic sequences are cut.

The authors designed a zinc-finger endonuclease meant to target the CCR5 gene and showed that it disrupts this gene in primary human T cells with very high specificity. When a mixture of modified and unmodified T cells was infected with HIV in a culture dish, the modified T cells survived better. Tests in a mouse model of HIV infection revealed that animals transplanted with the modified T cells had lower viral loads and higher numbers of T cells compared with animals that received unmodified T cells.

Ultimately, if clinical trials confirm the positive results in mice reported here, this treatment may be useful for restoring the immune systems of HIV-positive individuals by rendering their T cells resistant to HIV infection.

Author contact:

Carl June (University of Pennsylvania, Philadelphia, PA, USA)
E-mail: cjune@mail.med.upenn.edu

Abstract available online.

(C) Nature Biotechnology press release.

Message posted by: Trevor M. D'Souza