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CRISPR技术作为遗传疾病创新筛查和治疗工具的评估。

Appraisal of CRISPR Technology as an Innovative Screening to Therapeutic Toolkit for Genetic Disorders.

作者信息

Shahid Ayesha, Zahra Ambreen, Aslam Sabin, Shamim Amen, Ali Waqas Rafique, Aslam Bilal, Khan Sultan Habibullah, Arshad Muhammad Imran

机构信息

National Center for Genome Editing, Center for Advanced Studies/D-8 Research Center, University of Agriculture, Faisalabad, 38000, Pakistan.

Center for Agricultural Biochemistry and Biotechnology, University of Agriculture, Faisalabad, 38000, Pakistan.

出版信息

Mol Biotechnol. 2025 Feb 2. doi: 10.1007/s12033-025-01374-z.

DOI:10.1007/s12033-025-01374-z
PMID:39894889
Abstract

The high frequency of genetic diseases compels the development of refined diagnostic and therapeutic systems. CRISPR is a precise genome editing tool that offers detection of genetic mutation with high sensitivity, specificity and flexibility for point-of-care testing in low resource environment. Advancements in CRISPR ushered new hope for the detection of genetic diseases. This review aims to explore the recent advances in CRISPR for the detection and treatment of genetic disorders. It delves into the advances like next-generation CRISPR diagnostics like nano-biosensors, digitalized CRISPR, and omics-integrated CRISPR technologies to enhance the detection limits and to facilitate the "lab-on-chip" technologies. Additionally, therapeutic potential of CRISPR technologies is reviewed to evaluate the implementation potential of CRISPR technologies for the treatment of hematological diseases, (sickle cell anemia and β-thalassemia), HIV, cancer, cardiovascular diseases, and neurological disorders, etc. Emerging CRISPR therapeutic approaches such as base/epigenetic editing and stem cells for the development of foreseen CRIPSR drugs are explored for the development of point-of-care testing. A combination of predictive models of artificial intelligence and machine learning with growing knowledge of genetic disorders has also been discussed to understand their role in acceleration of genetic detection. Ethical consideration are briefly discussed towards to end of review. This review provides the comprehensive insights into advances in the CRISPR diagnostics/therapeutics which are believed to pave the way for reliable, effective, and low-cost genetic testing.

摘要

遗传疾病的高发性促使人们开发精准的诊断和治疗系统。CRISPR是一种精确的基因组编辑工具,能够以高灵敏度、特异性和灵活性检测基因突变,适用于资源匮乏环境下的即时检测。CRISPR技术的进步为遗传疾病的检测带来了新希望。本综述旨在探讨CRISPR在遗传疾病检测和治疗方面的最新进展。它深入研究了诸如纳米生物传感器等下一代CRISPR诊断技术、数字化CRISPR以及组学整合CRISPR技术等进展,以提高检测限并推动“芯片实验室”技术发展。此外,还综述了CRISPR技术的治疗潜力,以评估CRISPR技术在治疗血液疾病(镰状细胞贫血和β地中海贫血)、HIV、癌症、心血管疾病和神经系统疾病等方面的应用潜力。为了开发即时检测,还探索了新兴的CRISPR治疗方法,如碱基/表观遗传编辑和用于开发预期CRISPR药物的干细胞。还讨论了人工智能和机器学习的预测模型与对遗传疾病不断增长的认识相结合,以了解它们在加速基因检测中的作用。综述结尾简要讨论了伦理考量。本综述全面深入地介绍了CRISPR诊断/治疗的进展,相信这些进展将为可靠、有效且低成本的基因检测铺平道路。

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本文引用的文献

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Emerging Therapeutic Approaches and Genetic Insights in Stargardt Disease: A Comprehensive Review.新兴治疗方法和斯塔加特病的遗传见解:全面综述。
Int J Mol Sci. 2024 Aug 14;25(16):8859. doi: 10.3390/ijms25168859.
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Pomalidomide, bortezomib, and dexamethasone for newly diagnosed multiple myeloma patients with renal impairment.泊马度胺、硼替佐米及地塞米松用于新诊断的肾功能不全多发性骨髓瘤患者
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CRISPR/Cas9 technology: applications in oocytes and early embryos.
CRISPR/Cas9 技术:在卵母细胞和早期胚胎中的应用。
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Integrative omics approaches to advance rare disease diagnostics.综合组学方法推进罕见病诊断。
J Inherit Metab Dis. 2023 Sep;46(5):824-838. doi: 10.1002/jimd.12663.
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Genome-wide CRISPR screening of chondrocyte maturation newly implicates genes in skeletal growth and height-associated GWAS loci.全基因组CRISPR筛选软骨细胞成熟过程,新发现了与骨骼生长和身高相关全基因组关联研究(GWAS)位点中的基因。
Cell Genom. 2023 Apr 14;3(5):100299. doi: 10.1016/j.xgen.2023.100299. eCollection 2023 May 10.
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Editorial: CRISPR and beyond: Cutting-edge technologies for gene correction in therapeutic applications.社论:CRISPR及其他:治疗应用中基因校正的前沿技术
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CRISPR screening in cardiovascular research.心血管研究中的CRISPR筛选
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PAM-flexible Cas9-mediated base editing of a hemophilia B mutation in induced pluripotent stem cells.PAM灵活的Cas9介导的诱导多能干细胞中乙型血友病突变的碱基编辑。
Commun Med (Lond). 2023 Apr 19;3(1):56. doi: 10.1038/s43856-023-00286-w.
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Multimodal CRISPR perturbations of GWAS loci associated with coronary artery disease in vascular endothelial cells.多模态 CRISPR 干扰与血管内皮细胞中冠心病相关的 GWAS 位点。
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Therapeutic gene correction for Lesch-Nyhan syndrome using CRISPR-mediated base and prime editing.使用CRISPR介导的碱基编辑和引导编辑对莱施-奈恩综合征进行治疗性基因校正。
Mol Ther Nucleic Acids. 2023 Feb 14;31:586-595. doi: 10.1016/j.omtn.2023.02.009. eCollection 2023 Mar 14.