Novel Si RNA microbicides to prevent HIV-1 infectio

  • Herold, Betsy (PI)
  • Ramratnam, Bharat (PI)
  • McDonough, Joe A. (PI)
  • Lambert, Paul (PI)
  • Alexander, Kenneth (PI)
  • McDonough, Joe A. (PI)

Project: Research project

Project Details

Description

Heterosexual transmission accounts for the majority of new cases of HIV-1 infection each year. Recent[unreadable]
reports from the World Health Organization estimate that a total of 38 million people are now infected with[unreadable]
HIV-1 worldwide; 90% of whom live in developing countries. Nearly 50% of all infected individuals were[unreadable]
women. The increased incidence of HIV-1 infection in women, particularly those of childbearing age,[unreadable]
underscores the urgent need for effective preventative and therapeutic options that are safe, affordable and[unreadable]
culturally accepted. In the absence of an effective preventative vaccine, topical microbicides may offer a[unreadable]
practical alternative to block HIV-1 transmission at the site of entry. We seek funds to determine whether the[unreadable]
process of RNA interference (RNAi) can be harnessed to prevent the cervico-vaginal transmission of HIV-1[unreadable]
and thereby emerge as a novel microbicidal strategy. This work will be conducted by investigators at Rhode[unreadable]
Island Hospital, Brown University (B. Ramratnam) and Harvard-NEPRC (K. Mansfield). RNAi refers to the[unreadable]
sequence-specific degradation of RNA that follows the cellular introduction of homologous, short interfering[unreadable]
(si) RNA. We hypothesize that RNAi can be specifically targeted to the mucosal surfaces and decrease the[unreadable]
expression of host factors that mediate HIV-1/SIV mucosal transmission. For these proof-of-principle studies,[unreadable]
we will target the CCR5 chemokine receptor in macaques. We will pursue three specific aims over the 12-[unreadable]
month period. 1: To characterize the tissue penetrance of liposomal and nanaocapsule formulated siRNA[unreadable]
following direct mucosal application. 2: To quantify the kinetics and durability of mucosal CCR5 knockdown[unreadable]
following single and serial mucosal applications of siRNA. 3. To conduct virus challenge experiments in[unreadable]
siRNA treated animals. At the end of the granting period, we will have defined the HIV-1 microbicidal[unreadable]
potential of siRNA.
StatusFinished
Effective start/end date7/1/068/31/07

ASJC

  • Microbiology (medical)
  • Infectious Diseases
  • Genetics
  • Molecular Medicine
  • Molecular Biology
  • Cancer Research
  • Biotechnology
  • Virology
  • Pharmacology
  • Microbiology
  • Biomaterials
  • Pharmaceutical Science
  • Reproductive Medicine
  • Immunology