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

对培养细胞中HIV-1感染的有效抑制。我们将将这些结构的分析扩展到原代CD34+细胞和T淋巴细胞作为特定目标的一部分。在目标2中，进一步分析了HIV-1 RNA运输的功能作用通过核仁将被探索。具体而言，我们将调查2'0-甲基共价骨架修饰的可能性在HN-1 RNA的R区域中，由细胞小核仁RNA引导。我们将设计一个小核仁RNA，以误导2'0 HIV TAR和RL3E元素中蛋白质相互作用的特定位点的甲基化。最后，将开发一个体内SELEX方案为了选择新靶标，都使用核仁局部核酶的随机结合臂库中的HIV-1和细胞RNA。这在此目标中提出的工作的结果应扩展我们对HIV RNA和蛋白质运输的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TC 通过使用核酶来增强我们对HIV RNA定位的理解，并确定最佳的核酶HIV目标策略人类基因疗法的未来使用。我