设计广谱抗 HIV-1 gRNAs 以靶向患者来源的变异体。
Designing broad-spectrum anti-HIV-1 gRNAs to target patient-derived variants.
机构信息
Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.
Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.
出版信息
Sci Rep. 2017 Oct 31;7(1):14413. doi: 10.1038/s41598-017-12612-z.
Clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated protein 9 (Cas9), including specific guide RNAs (gRNAs), can excise integrated human immunodeficiency virus type 1 (HIV-1) provirus from host chromosomes. To date, anti-HIV-1 gRNAs have been designed to account for off-target activity, however, they seldom account for genetic variation in the HIV-1 genome within and between patients, which will be crucial for therapeutic application of this technology. This analysis tests the ability of published anti-HIV-1 gRNAs to cleave publicly available patient-derived HIV-1 sequences to inform gRNA design and provides basic computational tools to researchers in the field.
成簇规律间隔短回文重复序列（CRISPR）相关蛋白 9（Cas9），包括特定的向导 RNA（gRNA），可以从宿主染色体中切除整合的人类免疫缺陷病毒 1 型（HIV-1）前病毒。迄今为止，已经设计了抗 HIV-1 的 gRNA 来考虑脱靶活性，但是，它们很少考虑到患者内和患者间 HIV-1 基因组的遗传变异，这对于该技术的治疗应用至关重要。该分析测试了已发表的抗 HIV-1 gRNA 切割公开可用的源自患者的 HIV-1 序列的能力，以为 gRNA 设计提供信息，并为该领域的研究人员提供基本的计算工具。
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