Enhancing the Intracellular Functioning of anti-HIV RNAs

增强抗 HIV RNA 的细胞内功能

• 批准号: 7922925
• 负责人: John Joseph Rossi
• 金额: $ 71.1万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-21 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7922925
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adjuvant; Adverse effects; Anti-Retroviral Agents; Antisense RNA; Binding; Biological; CD34 gene; Catalytic RNA; Cell Nucleolus; Cell Transplants; Cells; Cessation of life; Clinical; Cultured Cells; Development; Disease; Dose; Drug resistance; Elements; Engineering; Engraftment; Epidemic; Fibroblasts; Frequencies; Funding; Future; Gene Targeting; Gene Therapy Agent; General Population; Genes; Genetic Transduction; Goals; Guide RNA; HIV; HIV Infections; HIV-1; Hematopoietic stem cells; Highly Active Antiretroviral Therapy; Human; Infection; Knowledge; Libraries; Life Cycle Stages; Methylation; Modification; Molecular; NOD/SCID mouse; Patients; Pharmaceutical Preparations; Population; Proteins; Protocols documentation; RNA; Rage; Randomized; Research; Role; Schedule; Scheme; Series; Site; Skin; Small Nucleolar RNA; T-Lymphocyte; Tars; Testing; Therapeutic; Toxic effect; Treatment Protocols; Upper arm; Variant; Vertebral column; Viral; Virus; Walkers; Work; aptamer; base; cellular transduction; chemotherapy; gene therapy; in vivo; protein transport; therapeutic gene; trafficking

potent inhibition of HIV-1 infection in cultured cells. We will extend our analyses of these constructs to primary CD34+ cells and T-lymphocytes as part of specific aim 1. In aim 2 further analyses of the functional role of HIV-1 RNA trafficking through the nucleolus will be explored. Specifically, we will investigate the possibility that 2'0-methyl covalent backbone modifications in the R region of HN-1 RNA are guided by a cellular small nucleolar RNA. We will engineer a small nucleolar RNA to misdirect 2'0 methylations to specific sites of protein interaction in the HIV TAR and Rl3E elements. Finally, an in vivo SELEX scheme will be developec to select for new targets, both in HIV-1 and cellular RNAs using a randomized binding arm library of nucleolar localized ribozymes. The results of the work proposed in this aim should extend our knowledge of the functional role of HIV RNA and protein trafficking through tht nucleolus, and provide new ribozymes and other inhibitory RNAs for inhibition of HIV-1 infection. The overall objective of this work is tc enhance our understanding of HIV RNA localization via the use of ribozymes, and to identify the best ribozyme-HIV target strategies for future use in human gene therapy. I

在培养细胞中有效抑制HIV-1感染。我们将把对这些结构的分析扩展到