Findings from L.A. Wheeler and Co-Authors Broaden Understanding of HIV/AIDS

According to the authors of a study from Boston, Massachusetts, "The continued spread of the HIV epidemic underscores the need to interrupt transmission. One attractive strategy is a topical vaginal microbicide."

"Sexual transmission of herpes simplex virus type 2 (HSV-2) in mice can be inhibited by intravaginal siRNA application. To overcome the challenges of knocking down gene expression in immune cells susceptible to HIV infection, we used chimeric RNAs composed of an aptamer fused to an siRNA for targeted gene knockdown in cells bearing an aptamer-binding receptor. Here, we showed that CD4 aptamer-siRNA chimeras (CD4-AsiCs) specifically suppress gene expression in CD4(+) T cells and macrophages in vitro, in polarized cervicovaginal tissue explants, and in the female genital tract of humanized mice. CD4-AsiCs do not activate lymphocytes or stimulate innate immunity. CD4-AsiCs that knock down HIV genes and/or CCR5 inhibited HIV infection in vitro and in tissue explants. When applied intravaginally to humanized mice, CD4-AsiCs protected against HIV vaginal transmission," wrote L.A. Wheeler and colleagues.

The researchers concluded: "Thus, CD4-AsiCs could be used as the active ingredient of a microbicide to prevent HIV sexual transmission."

Wheeler and colleagues published their study in the Journal of Clinical Investigation (Inhibition of HIV transmission in human cervicovaginal explants and humanized mice using CD4 aptamer-siRNA chimeras. Journal of Clinical Investigation, 2011;121(6):2401-2412).

The Friends of AIDS Foundation is dedicated to enhancing the quality of life for HIV positive individuals and empowering people to make healthy choices to prevent the spread of the HIV virus. To learn more about The Friends of AIDS Foundation, please visit: http://www.friendsofaids.org.


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