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综述:利用CRISPR-cas系统进行基因组和转录组编辑用于血液系统恶性肿瘤的基因治疗

Mini review: genome and transcriptome editing using CRISPR-cas systems for haematological malignancy gene therapy.

作者信息

Elliott Esther K, Haupt Larisa M, Griffiths Lyn R

机构信息

Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Ave, Kelvin Grove, QLD, 4059, Australia.

出版信息

Transgenic Res. 2021 Apr;30(2):129-141. doi: 10.1007/s11248-020-00232-9. Epub 2021 Feb 20.

Abstract

The recent introduction of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated protein (Cas) systems, offer an array of genome and transcriptome editing tools for clinical repair strategies. These include Cas9, Cas12a, dCas9 and more recently Cas13 effectors. RNA targeting CRISPR-Cas13 complexes show unique characteristics with the capability to engineer transcriptomes and modify gene expression, providing a potential clinical cancer therapy tool across various tissue types. Cas13 effectors such as RNA base editing for A to I replacement allows for precise transcript modification. Further applications of Cas13a highlights its capability of producing rapid diagnostic results in a mobile platform. This review will focus on the adaptions of existing CRISPR-Cas systems, along with new Cas effectors for transcriptome or RNA modifications used in disease modelling and gene therapy for haematological malignancy. We also address the current diagnostic and therapeutic potential of CRISPR-Cas systems for personalised haematological malignancy.

摘要

近期引入的成簇规律间隔短回文重复序列(CRISPR)及CRISPR相关蛋白(Cas)系统,为临床修复策略提供了一系列基因组和转录组编辑工具。这些工具包括Cas9、Cas12a、dCas9以及最近的Cas13效应蛋白。靶向RNA的CRISPR-Cas13复合物具有独特特性,能够对转录组进行改造并修饰基因表达,为跨多种组织类型的潜在临床癌症治疗提供了工具。诸如用于将A替换为I的RNA碱基编辑等Cas13效应蛋白可实现精确的转录本修饰。Cas13a的进一步应用凸显了其在移动平台上产生快速诊断结果的能力。本综述将聚焦于现有CRISPR-Cas系统的适应性改造,以及用于疾病建模和血液系统恶性肿瘤基因治疗的、用于转录组或RNA修饰的新型Cas效应蛋白。我们还探讨了CRISPR-Cas系统在个性化血液系统恶性肿瘤方面当前的诊断和治疗潜力。

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