The HIV epidemic is continuing spread and efforts to develop a vaccine that protects against infection are still showing limited promise. Therefore, researchers are seeking to develop alternative approaches to block HIV transmission. One such strategy is vaginal application of an agent known as a microbicide, which works to kill the virus at the site of entry into the body. A team of researchers, led by Judy Lieberman, at Harvard Medical School, Boston, has now developed a new agent that they hope could be used as the active ingredient in a microbicide to prevent HIV transmission.
HIV infects cells in the body that express the protein CD4. Lieberman and colleagues generated CD4 aptamers (a structured RNA that binds CD4 with high affinity) fused to small inhibitory RNAs targeting the HIV gag or vif genes (which template essential HIV proteins) or the human CCR5 gene (which templates a protein key to HIV entry into cells). These chimeric aptamers were taken up by CD4+ cells, where they knocked down expression of their target genes. More importantly, they inhibited HIV infection of primary CD4+ cells in vitro and of CD4+ cells in polarized human cervicovaginal explants. Furthermore, when applied vaginally to humanized mice they protected against vaginal transmission of HIV. Although additional studies are required to determine how long gene silencing and protection lasts, these data suggest that microbicides containing CD4 aptamers fused to defined small inhibitory RNAs could provide a new tool in the fight against HIV/AIDS.
TITLE: Inhibition of HIV transmission in human cervicovaginal explants and humanized mice using CD4 aptamer-siRNA chimeras
AUTHOR CONTACT:
Judy Lieberman
Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
Phone: 617.713.8600; Fax: 617.713.8620; E-mail: lieberman@idi.harvard.edu .
View this article at: http://www.jci.org/articles/view/45876?key=f00cbc583fd015db1899
Journal of Clinical Investigation