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基因组编辑工具的作用机制及其在遗传遗传性疾病中的应用

Mechanism of Genome Editing Tools and Their Application on Genetic Inheritance Disorders.

作者信息

Oh Dae Hwan

机构信息

Institute of Green Manufacturing Technology, Korea University, Seoul, Republic of Korea.

出版信息

Glob Med Genet. 2024 Sep 16;11(4):319-329. doi: 10.1055/s-0044-1790558. eCollection 2024 Dec.

Abstract

In the fields of medicine and bioscience, gene editing is increasingly recognized as a promising therapeutic approach for treating pathogenic variants in humans and other living organisms. With advancements in technology and knowledge, it is now understood that most genetic defects are caused by single-base pair variants. The ability to substitute genes using genome editing tools enables scientists and doctors to cure genetic diseases and disorders. Starting with CRISPR (clustered regularly interspaced short palindromic repeats)/Cas, the technology has evolved to become more efficient and safer, leading to the development of base and prime editors. Furthermore, various approaches are used to treat genetic disorders such as hemophilia, cystic fibrosis, and Duchenne muscular dystrophy. As previously mentioned, most genetic defects leading to specific diseases are caused by single-base pair variants, which can occur at many locations in corresponding gene, potentially causing the same disease. This means that, even when using the same genome editing tool, results in terms of editing efficiency or treatment effectiveness may differ. Therefore, different approaches may need to be applied to different types of diseases. Prevalently, due to the safety of adeno-associated virus (AAV) vectors in gene therapy, most clinical trials of gene therapy are based on AAV delivery methods. However, despite their safety and nonintegration into the host genome, their limitations, such as confined capacity, dosage-dependent viral toxicity, and immunogenicity, necessitate the development of new approaches to enhance treatment effects. This review provides the structure and function of each CRISPR-based gene editing tool and focuses on introducing new approaches in gene therapy associated with improving treatment efficiency.

摘要

在医学和生物科学领域,基因编辑越来越被认为是一种有前景的治疗方法,可用于治疗人类和其他生物体中的致病变异。随着技术和知识的进步,现在人们了解到大多数基因缺陷是由单碱基对变异引起的。使用基因组编辑工具替代基因的能力使科学家和医生能够治愈遗传疾病和病症。从CRISPR(成簇规律间隔短回文重复序列)/Cas开始,这项技术已经发展得更加高效和安全,从而催生了碱基编辑器和引导编辑器的发展。此外,还采用了各种方法来治疗诸如血友病、囊性纤维化和杜兴氏肌肉营养不良等遗传疾病。如前所述,导致特定疾病的大多数基因缺陷是由单碱基对变异引起的,这些变异可能发生在相应基因的许多位置,有可能导致同一种疾病。这意味着,即使使用相同的基因组编辑工具,编辑效率或治疗效果方面的结果也可能不同。因此,可能需要针对不同类型的疾病采用不同的方法。目前,由于腺相关病毒(AAV)载体在基因治疗中的安全性,大多数基因治疗临床试验都基于AAV递送方法。然而,尽管它们具有安全性且不会整合到宿主基因组中,但其局限性,如容量有限、剂量依赖性病毒毒性和免疫原性,使得有必要开发新的方法来提高治疗效果。本综述介绍了每种基于CRISPR的基因编辑工具的结构和功能,并着重介绍了与提高治疗效率相关的基因治疗新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b067/11405120/d2e1dd05ad2e/10-1055-s-0044-1790558-i2400065-1.jpg

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