Enhancing the Intracellular Functioning of anti-HIV RNAs

增强抗 HIV RNA 的细胞内功能

基本信息

批准号：
8128036
负责人：
John Joseph Rossi
金额：
$ 18.76万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-23 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8128036
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 Regimen Research Role Schedule Scheme Series Site Skin Small Nucleolar RNA T-Lymphocyte Tars Testing Therapeutic Toxic effect Variant Vertebral column Viral Virus Walkers Work aptamer arm base cellular transduction chemotherapy gene therapy in vivo protein transport therapeutic gene trafficking

项目摘要

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

有效抑制培养细胞中的 HIV-1 感染。我们将对这些结构的分析扩展到原代 CD34+ 细胞和 T 淋巴细胞作为具体目标 1 的一部分。目标 2 进一步分析 HIV-1 RNA 运输的功能作用将探索通过核仁。具体来说，我们将研究 2'0-甲基共价主链修饰的可能性 HN-1 RNA 的 R 区由细胞小核仁 RNA 引导。我们将设计一个小的核仁 RNA 来误导 2'0 HIV TAR 和 R13E 元件中蛋白质相互作用特定位点的甲基化。最后，将开发体内SELEX方案使用核仁定位核酶的随机结合臂库选择 HIV-1 和细胞 RNA 中的新靶点。这该目标中提出的工作结果应扩展我们对 HIV RNA 和蛋白质贩运功能作用的了解。核仁，并提供新的核酶和其他抑制性RNA来抑制HIV-1感染。这项工作的总体目标是通过使用核酶增强我们对 HIV RNA 定位的理解，并确定最佳的核酶-HIV 靶向策略未来在人类基因治疗中的应用。我