CRISPR/Cas9 technology toward understanding HIV latency in primary cells

CRISPR/Cas9 技术有助于了解原代细胞中的 HIV 潜伏期

基本信息

批准号：
9203550
负责人：
VICENTE PLANELLES
金额：
$ 22.65万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9203550
关键词：
Adverse effects Attenuated Biochemical Biochemical Pathway Biological Biological Assay CRISPR/Cas technology Candidate Disease Gene Cell Survival Cell model Cells Clustered Regularly Interspaced Short Palindromic Repeats Development Drug resistance Exploratory/Developmental Grant for Diagnostic Cancer Imaging Foundations Gene Proteins Genes Genetic Genetic Screening Genetic Transcription Genetic screening method Genome engineering Goals HIV HIV Infections HIV-1 Immune system Immunologic Deficiency Syndromes In Vitro Individual Infection Interruption Laboratories Lead Lymphocyte Maintenance Memory Modeling Outcome Pathway interactions Patients Proviruses Publishing Reagent Regulator Genes Seeds Small Interfering RNA T-Lymphocyte Technology Testing Therapeutic Agents Toxic effect Transformed Cell Line Validation Viral Viremia Virion Virus Virus Latency antiretroviral therapy base cell transformation cost cytokine feeding genetic manipulation genome-wide analysis in vivo knock-down novel novel therapeutics programs protein complex reactivation from latency small hairpin RNA targeted treatment tat Protein tool vector

项目摘要

The presence of latent HIV in individuals treated with highly active combination antiretroviral therapy (cART) has been well established. Without additional therapies, individuals must remain on ART indefinitely in order to avoid development of severe immunodeficiency and spread of the virus. Because of the existence of this reservoir, treatment interruption invariably leads to viral rebound. Thus, it is generally accepted that eradication of the virus will require elimination of the latent reservoir. The fundamental goal of this proposal is adapt our primary TCM-based assay for HIV-1 latency described above to be amenable for testing of latency regulator genes via CRISPR/Cas9 technology. Our initial targets will therefore be candidate genes that are widely accepted to be important for either the establishment/maintenance of latency or for reactivation from latency, and a number of previously untested genes that were identified through genetic screens in various laboratories. Successful validation of novel genes/proteins that control viral latency will lead to identification of relevant pathways and mechanistic studies that will have the potential to spawn major new initiatives to develop novel therapeutics.

用高活性组合抗逆转录病毒疗法治疗的个体中潜在艾滋病毒的存在（购物车）已经建立了良好。如果没有其他疗法，个人必须无限期地保持艺术为了避免发育严重的免疫缺陷和病毒传播。由于存在这种储层，治疗中断总是导致病毒反弹。因此，人们普遍认为根除病毒将需要消除潜在储层。该提案的基本目标是调整我们基于TCM的HIV-1潜伏期的主要测定法上面描述的是通过CRISPR/CAS9技术测试潜伏期调节子基因的适合。我们的因此，初始靶标将是候选基因，被广泛接受为重要延迟的延迟或延迟重新激活，以及许多先前未经测试的通过各种实验室中的遗传筛选鉴定的基因。成功验证控制病毒潜伏期的新型基因/蛋白质将导致鉴定相关的途径和机械研究，有可能产生重大的新计划开发新颖的治疗学。