Of viral life cycle 2distinct anti hiv mechanisms

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of viral life cycle 2.Distinct anti-HIV mechanisms Goals 1.Inhibit multiple HIVs CCR5 tropic HIVs CXCR4 tropic HIVs Multi-drug resistant HIVs 2.Prevent emergence of resistant HIV mutants CCR5-siRNA Hu-TRIMcyp C46 entry inhibitor HIV TCR
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Engineered Immunity” Stem cell based approaches Would allow direct genetic modification of progenitor (“baby”) cells in the body Would allow prolonged self-renewal of modified cells that would have long life in the body Cells would undergo normal development and be recognized as part of the body
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Goal: We are interested in using molecularly cloned, HIV- specific T cell receptors (TCRs) from HIV-specific CD8+ T cells and other HIV-targeting molecules to modify human blood forming stem cells to target and kill HIV in infected individuals Engineering Antiviral Immunity
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Virus Infected cells Virus Infected cells T cell TCR TCR Stem cell Stem cell Viral Vectors Containing Cloned TCRs T cell T cell T cell T cell T cell T cell T cell T cell “Genetic Vaccination” to HIV TCR TCR TCR TCR TCR TCR
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CD34+ CD34+ CD34+ CD34+ CD34+ 1. Sort CD34+ 6. Analyze TCR Expression/F unction 6-12 weeks Fetal Liver 2. Transduce with Anti-HIV TCR or Control TCR HLA-A*0201+ Tissue 3. Combine with fetal thymus tissue and liver stroma, implant under kidney capsule 2a. Viably freeze fraction CD34+ CD34+ CD34+ 4. Thaw and Transduce with Anti-HIV TCR Or Control TCR
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