Viral Gene Editing and Bioinformatics Core for Institution # 269291

总结 病毒基因编辑和生物信息学核心（VGEBC）的总体目标是提供基础和临床 研究人员的知识和熟悉的最新技术，涉及遗传方法，包括 基因编辑研究HIV的神经科学，探索抑制病毒感染的新策略。 VGEBC将提供全面和综合的CRISPR基因编辑设计， 执行管道。我们的合作，多机构专家团队将提供指导，培训和 共享资源，使CRISPR技术在专注于更好地 了解neuroHIV的机制，发现可靠的生物标志物用于早期诊断， 开发智能疗法以治愈疾病。这些服务将包括规范的DNA编辑器：SpCas 9和 SaCas 9、新型CasX和CasY、RNA编辑Cas 13和使用CRISPR介导的基因表达调控 在一个实施方案中，所述载体包含与多种效应子结构域融合的催化死亡的Cas9（dCas 9）。此外，核心将测试和 对现有的和新的基因编辑器进行新的升级，因为它们从文献中出现。设计和 最佳gRNA的选择将在联合主任及其生物信息学团队的协助下进行。 The Core在基因编辑、生物信息学序列分析和基因递送方面的独特专长，以及跨 两所大学之间的合作将用于指导研究人员：i）设计最新的 和安全的基因编辑技术; ii）利用最新的生物信息学管道， 最大限度地减少脱靶效应; iii）激活或抑制基因转录的发展策略; iv） 采用最准确和最具成本效益的基因组测序与长读技术。我们的核心 将与CNHC的其他核心密切合作，促进全面，协同，多学科 合作计划。原代患者来源的细胞将通过临床和转化 研究支持核心（CTRSC）与NeuroHIV社区伙伴关系和差异核心 （NHCPDC）;细胞系和细胞培养模型将通过细胞生物学和功能 核心分析（CBFAC）。生物统计支持将通过中央行政和 管理核心（CAMC）。我们将通过互动为试点项目获奖者提供专业知识和服务 发展研究和指导核心（DRMC）。这种协同增效的办法将确保 CNHC发展奖获得者和用户在开展富有成效的高影响力研究方面的成功 在神经艾滋病研究中。

SUMMARY The overall objective of the Viral Gene Editing and Bioinformatics Core (VGEBC) is to provide basic and clinical researchers with knowledge and familiarity with the latest technology involving a genetic approach, including gene editing to investigate the neuroscience of HIV and exploring novel strategies for suppressing viral infection. The VGEBC will offer access to a comprehensive and integrated CRISPR gene editing design and implementation pipeline. Our collaborative, multi-institutional team of experts will provide guidance, training and shared resources allowing successful utilization of the CRISPR technology in projects focused on a better understanding of the mechanisms of neuroHIV and the discovery of reliable biomarkers for early diagnosis and development of intelligent therapies toward a cure. The services will include canonical DNA editors: SpCas9 and SaCas9, novel CasX and CasY, RNA editing Cas13, and CRISPR-mediated gene expression regulation using catalytically dead Cas9 (dCas9) fused to a variety of effector domains. Additionally, the Core will test and implement new upgrades to existing and novel gene editors as they emerge from the literature. The design and selection of optimal gRNAs will be performed with the assistance of the co-director and his bioinformatics team. The Core's unique expertise in gene editing, bioinformatics sequence analysis, and gene delivery, and the cross- collaboration between two universities will be used to guide investigators in: i) the design of the most up-to-date and safe gene-editing techniques; ii) the utilization of the latest bioinformatic pipeline to maximize in target and minimize off-target effects; iii) the development strategies for activation or suppression of gene transcription; iv) the employment the most accurate and cost-effective genomic sequencing with long-read technology. Our Core will work closely with the other cores of the CNHC to promote a comprehensive, synergistic, multidisciplinary collaborative program. Primary patient-derived cells will be available through the Clinical and Translational Research Support Core (CTRSC) in conjunction with the NeuroHIV Community Partnership and Disparity Core (NHCPDC); and cell lines and cell culture models will be available through the Cell Biology and Functional Analyses Core (CBFAC). Biostatistical support will be provided through the Central Administrative and Management Core (CAMC). We will provide expertise and services to pilot project awardees through interactions with the Developmental Research and Mentorship Core (DRMC). This synergistic approach will ensure the success of the CNHC developmental award recipients and users in conducting productive high-impact research in neuroHIV research.