This project is a response to a call for proposals to develop novel microbicides to prevent HIV-1 infection. Although limited successes have hinted at the promise of microbicide-based prevention, the mixed results of clinical trials underscore the significant shortcomings of simple gel approaches, which depend on intermittent application and passive diffusion for nonspecific drug delivery. We have assembled a multidisciplinary team of investigators to address major issues required for an effective microbicide: aqueous delivery of potent lipophilic drugs, anatomic localization, relevant cell targeting, intracellular localizaton, and sustained activity after application. These issues are approached through three aims focused on the highest risk site of HIV-1 acquisition (the colorectal mucosa):
Aim 1 : Novel polypeptide hydrogels with tunable properties will be adapted to persist and adhere to mucosa, as well as capture HIV-1 particles.
Aim 2 : Human "vault" bioparticles will be modified as carriers for nonpolar antiretroviral drugs, with specific targeting to release the drug payload intracytoplasmically into relevant cell types.
Aim 3 : Polymer chemistry will be applied to load the hydrogels with the vaults in a manner to provide sustained release and delivery of drugs into the relevant cell types for HIV-1 acquisition. These studies will provide a path to a safe, effective, and inexpensive microbicide for HIV-1 prevention.

Public Health Relevance

Given the lack of a truly useful vaccine and the intrinsic limitations of behavior-based prevention of HIV-1 acquisition, a safe and effective microbicide would offer an important strategy. This project provides a path forward using state-of-the-art technology to create a convenient, effective, and affordable microbicide

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI112016-01
Application #
8711813
Study Section
Special Emphasis Panel (ZAI1-JKB-A (J1))
Program Officer
Turpin, Jim A
Project Start
2014-03-01
Project End
2017-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$598,312
Indirect Cost
$205,169
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095