Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea.
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, Gangwon-Do 24252, Republic of Korea.
Mol Ther. 2021 Feb 3;29(2):571-586. doi: 10.1016/j.ymthe.2020.09.028. Epub 2020 Sep 20.
At present, the idea of genome modification has revolutionized the modern therapeutic research era. Genome modification studies have traveled a long way from gene modifications in primary cells to genetic modifications in animals. The targeted genetic modification may result in the modulation (i.e., either upregulation or downregulation) of the predefined gene expression. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated nuclease 9 (Cas9) is a promising genome-editing tool that has therapeutic potential against incurable genetic disorders by modifying their DNA sequences. In comparison with other genome-editing techniques, CRISPR-Cas9 is simple, efficient, and very specific. This enabled CRISPR-Cas9 genome-editing technology to enter into clinical trials against cancer. Besides therapeutic potential, the CRISPR-Cas9 tool can also be applied to generate genetically inhibited animal models for drug discovery and development. This comprehensive review paper discusses the origin of CRISPR-Cas9 systems and their therapeutic potential against various genetic disorders, including cancer, allergy, immunological disorders, Duchenne muscular dystrophy, cardiovascular disorders, neurological disorders, liver-related disorders, cystic fibrosis, blood-related disorders, eye-related disorders, and viral infection. Finally, we discuss the different challenges, safety concerns, and strategies that can be applied to overcome the obstacles during CRISPR-Cas9-mediated therapeutic approaches.
目前，基因组修饰的理念已经彻底改变了现代治疗研究时代。基因组修饰研究已经从原代细胞中的基因修饰发展到了动物中的基因修饰。靶向基因修饰可能导致预设基因表达的调节（即上调或下调）。成簇规律间隔短回文重复（CRISPR）-CRISPR 相关核酸酶 9（Cas9）是一种很有前途的基因组编辑工具，通过修饰其 DNA 序列，具有治疗不可治愈的遗传疾病的潜力。与其他基因组编辑技术相比，CRISPR-Cas9 简单、高效且非常特异。这使得 CRISPR-Cas9 基因组编辑技术能够进入针对癌症的临床试验。除了治疗潜力外，CRISPR-Cas9 工具还可用于生成遗传抑制的动物模型，用于药物发现和开发。本文全面综述了 CRISPR-Cas9 系统的起源及其对各种遗传疾病（包括癌症、过敏、免疫性疾病、杜氏肌营养不良症、心血管疾病、神经退行性疾病、肝脏相关疾病、囊性纤维化、血液相关疾病、眼部疾病和病毒感染）的治疗潜力。最后，我们讨论了 CRISPR-Cas9 介导的治疗方法中可能遇到的不同挑战、安全性问题以及可以应用的策略，以克服障碍。
