This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Replacing """"""""bad"""""""" DNA or treating patients with therapeutic DNA represents a promising approach to treating inherited as well as infectious diseases. Human Immunodeficiency Virus (HIV)-induced AIDS occurs in the cells designed to protect our bodies from disease, our immune cells. Our lab aims to direct gene therapy specifically to these cells to reduce HIV replication and slow the progress to AIDS. Current HIV therapy relies on high doses of drugs that suppress immune cells as a means to block the replication sites of HIV;however, these drugs compromise the patient's immune system. Targeting genetic material that would reduce immune cells specifically involved in HIV replication is desired. Gene delivery vehicles based on viruses or liposomes (small lipid envelopes) are attractive in terms of their ability to target and infect cells with therapeutic DNA, but typically initiate an immune response and are often toxic. Our goal is to develop DNA delivery vehicles that safely and effectively deliver DNA to immune cells by using FDA approved materials such as poly(DL-lactic-co-glycolic acid) or small peptides. Ultimately, these safe materials must be endowed with properties that facilitate the delivery of DNA to immune cells. Initial studies focus on screening different formulations of DNA delivery vehicles with immune cells (macrophages and T-cells) to determine optimal formulations for DNA delivery. Selected formulations will then be evaluated in mice modeling HIV-induced AIDS.
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