This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Currently, more than 40 Million people worldwide are persistently infected with HIV-1. Similar to HIV infection in humans, SIV infection in Asian macaques results in chronic disease that culminates in AIDS. The well-defined SIV infection of rhesus macaques closely resembles many aspects of HIV infection in humans including events associated with transmission, cellular tropism of the virus, viral replication patterns, disease progression, and the nature of the host immune response. Furthermore, the SIV/macaque model is important because knowledge of the time, route, and number of viral exposures is known, the viral stock used to infect the macaques is well-characterized, and there is the ability to frequently sample important tissues (blood, lymph nodes, mucosal sites, etc) throughout infection. One of the current main lines of research in the field of AIDS is the identification of new treatments that will result in reduction or suppression of viral loads in infected individuals. The goal of this project is to determine the in vivo efficacy of biodegradable poly (lactic-co-glycolic acid) polymers (PLGA) nanoparticles that carry small interfering RNAs (siRNAs) specific for SIVmac. In order to target mainly infected cells, the particles will also be coated with anti-CD4 antibodies. This study will use rhesus macaques already infected with SIV. The animals proposed for the first year of the project are already available from other studies performed by our laboratory. For subsequent years we propose to use animals from other AIDS projects at SNPRC (such as vaccine projects) that become infected with SIV and are scheduled for euthanasia. Thus, we will not increase the use of na[unreadable]ve animals;rather, we will increase the scientific value of animals that otherwise would be scheduled for euthanasia. If the results of these studies are successful, these biodegradable nanoparticles could be used in humans as an addition to traditional antiviral therapy, or for the design of topical microbicides.