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.