Eliminating the latent reservoir by targeted in vivo delivery of HIV-specific CARs

通过体内靶向递送 HIV 特异性 CAR 消除潜在病毒库

• 批准号: 10593735
• 负责人: Hamideh Parhiz
• 金额: $ 68.92万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-06 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10593735
• 关键词: Antibodies; Area; B-Lymphocytes; CD4 Positive T Lymphocytes; COVID-19 vaccine; CXCR4 gene; Cells; Clinic; Complex; Development; Effectiveness; Encapsulated; Environment; Exclusion; FDA approved; Genetic; Gills; Goals; HIV; HIV Infections; Half-Life; Immune; Immune system; Immunotherapy; In Vitro; Individual; Injectable; Lead; Length; Macrophage; Messenger RNA; Modeling; Nucleosides; Persons; Phase I Clinical Trials; Pilot Projects; Proteins; RNA; Research Personnel; Resistance; Site; T-Lymphocyte; Technology; Testing; Therapeutic; Therapeutic Agents; Tissues; Vertebral column; Viral reservoir; Viremia; Virus; antiretroviral therapy; cell type; design; experimental study; humanized mouse; immune clearance; in vivo; lipid nanoparticle; lymph nodes; manufacture; monocyte; nonhuman primate; reproductive; success; targeted delivery; tool; trafficking; vaccine delivery

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.

项目总结