Eliminating the latent reservoir by targeted in vivo delivery of HIV-specific CARs
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Principal Investigator: Hamideh Parhiz Organization: UNIVERSITY OF PENNSYLVANIA Fiscal Year: 2023 Award: $689,181 Funding agency: National Institute of Allergy and Infectious Diseases Project Summary For HIV cure approaches to be widely implemented, they will need to be safe, affordable and highly effective. The development strategies that allow therapeutic agents to be infused into people living with HIV (PLWH) rather than being manufactured ex vivo may represent an important step to reaching this goal. In this application, the investigators merged their expertise in mRNA lipid nanoparticles (mRNA-LNPs) and HIV CAR technology to propose to develop injectable agents that will target and remove the latent reservoir. A key advantage of this approach is that we can target tissues and cells such as the reproductive track or T follicular cells where CTLs are either excluded or have diminished activity. In Aim 1, we will optimize the composition of these mRNA-LNPs performing in vitro studies. Once lead compounds are identified, we will test these in humanized mouse for in vivo activity. Finally, using a state of the art non-human primate model we will test the ability of mRNA-LNP complexes to reduce the viral reservoir. Terms: <2019-nCoV vaccine><AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Antibodies><Area><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Blood monocyte><Body Tissues><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><COVID-19 vaccine><COVID19 vaccine><CXC-R4><CXCR-4><CXCR4><CXCR4 gene><Cell Body><Cells><Clinic><Complex><D2S201E><Development><Early-Stage Clinical Trials><Effectiveness><Encapsulated><Environment><Exclusion><FB22><FDA approved><Genetic><Gills><Goals><HIV><HIV Infections><HM89><HSY3RR><HTLV-III Infections><HTLV-III-LAV Infections><Half-Life><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><Immune><Immune mediated therapy><Immune system><Immunes><Immunologically Directed Therapy><Immunotherapy><In Vitro><Individual><Injectable><Investigators><LAP3><LAV-HTLV-III><LCR1><LESTR><Lead><Length><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphadenopathy-Associated Virus><Lymphatic nodes><Macrophage><Marrow monocyte><Messenger RNA><Modeling><Mφ><NPY3R><NPYR><NPYRL><NPYY3R><Non-Polyadenylated RNA><Nucleosides><Pb element><Persons><Phase 1 Clinical Trials><Phase I Clinical Trials><Pilot Projects><Proteins><RNA><RNA Gene Products><Research Personnel><Researchers><Resistance><Ribonucleic Acid><SARS-CoV-2 vaccine><SARS-CoV2 vaccine><SARS-coronavirus-2 vaccine><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe acute respiratory syndrome coronavirus 2 vaccine><Site><Spinal Column><Spine><T-Cells><T-Lymphocyte><T4 Cells><T4 Lymphocytes><Technology><Testing><Therapeutic><Therapeutic Agents><Tissues><Vertebral column><Viral reservoir><Viremia><Virus><Virus reservoir><Virus-HIV><anti-retroviral therapy><anti-retroviral treatment><antiretroviral therapy><antiretroviral treatment><backbone><cell type><corona virus disease 2019 vaccine><coronavirus disease 2019 vaccine><coronavirus disease-19 vaccine><deliver vaccines><design><designing><developmental><experiment><experimental research><experimental study><experiments><heavy metal Pb><heavy metal lead><humanized mice><humanized mouse><immune clearance><immune elimination><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><in vivo><lipid based nanoparticle><lipid nanoparticle><lymph gland><lymph nodes><lymphnodes><mRNA><manufacture><monocyte><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><non-human primate><nonhuman primate><phase I protocol><pilot study><reproductive><resistant><site targeted delivery><success><targeted delivery><thymus derived lymphocyte><tool><trafficking><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine delivery><vaccine for novel coronavirus><viraemia><viral sepsis><virusemia>