? The overall hypothesis to be tested in this proposal is that small interfering RNAs directed to HIV-1 can serve as a therapy for HIV-1 disease. RNA interference is an evolutionarily conserved mechanism whereby small double stranded RNAs induce sequence specific silencing of homologous genes. The application of siRNA technology consists of chemical or recombinant 21- 29 nucleotide length double strand RNAs that act to degrade the RNA template to which it has homology, siRNAs have been utilized for """"""""knock-out"""""""" of various cellular genes. Recently siRNA directed to HIV-1 sequences have been shown to inhibit HIV-1 replication in cell culture. Other """"""""genetic immunization"""""""" approaches to HIV-1 disease successfully inhibited HIV-1 in cell culture, but extension of the studies to humans had resulted in minimal efficacy. It is unclear whether the lack of success is due to the gene therapeutic reagent itself, the delivery system, or both. Thus, it is critical that genetic immunization approaches be thoroughly modeled in systems where variables can be tested and optimized to gain an understanding of the most effective parameters for inhibition. We propose to model siRNA to HIV-1 and CCR5 using lentiviral vectors for stable delivery. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI055281-04
Application #
7020735
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Voulgaropoulou, Frosso
Project Start
2003-03-01
Project End
2008-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
4
Fiscal Year
2006
Total Cost
$297,833
Indirect Cost
Name
University of California Los Angeles
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095