Ms. Sidi Yang
Faculty of Pharmacy, University of Manitoba
Development and characterization of a novel siRNA-based intravaginal nanomedicine: HIV/AIDS is considered as one of the most significant global health concerns of the 21st century. Despite successful HIV prevention strategies such as condom use, monogamy, and abstinence, HIV is a disease that has affected over 65,000 Canadians in 2009, with over 4,000 new HIV infections occurring each year in Canada. Current HIV incidence appears to have a disproportionate impact on women. Latest data reveals that women account for more than half of the infected population with unprotected sexual intercourse as the major mode of HIV transmission. In the absence of a HIV vaccine, we believe that microbicides (products designed for vaginal or rectal application for the purpose of reducing sexually transmitted infections, including HIV) are an excellent alternative to condoms to help reduce male-to-female transmission of HIV. Autophagy is a lysosomal degradation system in which damaged organelles, long-lived proteins and pathogens (i.e. viruses and bacteria) are degraded. Studies have shown that the HIV accessory protein negative factor (Nef) acts as an inhibitor of autophagy, thus preventing the elimination of HIV. Inhibition of Nef gene expression by RNA interference (a process whereby siRNA is introduced into the cytoplasm to modulate the cleavage of target RNA) has been shown to inhibit HIV production. Therefore, knocking down Nef expression may be an effective strategy to prevent HIV infection. The main objective of this research project is to develop a novel, intravaginal nanomedicine for preventing HIV infection during sexual intercourse. In brief, nanomedicines containing siRNAs will be developed and characterized. The optimal physico-chemical properties that provide necessary release, stability, and efficacy will be determined. In vitro transfection efficiency and cytotoxicity will also be evaluated. Lastly, the nanomedicine will be formulated into a vaginal gel to increase drug retention and improve user adherence.