Centre de Recherche du CHU de Québec-Université Laval, Quebec City, QC G1V 4G2, Canada.
Department of Molecular Medicine, Faculty of Medicine, Laval University, Quebec City, QC G1V 0A6, Canada.
Cells. 2023 Feb 7;12(4):536. doi: 10.3390/cells12040536.
Gene therapy holds tremendous potential in the treatment of inherited diseases. Unlike traditional medicines, which only treat the symptoms, gene therapy has the potential to cure the disease by addressing the root of the problem: genetic mutations. The discovery of CRISPR/Cas9 in 2012 paved the way for the development of those therapies. Improvement of this system led to the recent development of an outstanding technology called prime editing. This system can introduce targeted insertions, deletions, and all 12 possible base-to-base conversions in the human genome. Since the first publication on prime editing in 2019, groups all around the world have worked on this promising technology to develop a treatment for genetic diseases. To date, prime editing has been attempted in preclinical studies for liver, eye, skin, muscular, and neurodegenerative hereditary diseases, in addition to cystic fibrosis, beta-thalassemia, X-linked severe combined immunodeficiency, and cancer. In this review, we portrayed where we are now on prime editing for human gene therapy and outlined the best strategies for correcting pathogenic mutations by prime editing.
基因治疗在治疗遗传性疾病方面具有巨大的潜力。与仅治疗症状的传统药物不同，基因治疗有可能通过解决根本问题——基因突变来治愈疾病。2012 年 CRISPR/Cas9 的发现为这些疗法的发展铺平了道路。该系统的改进导致了最近一种名为 prime editing 的杰出技术的发展。该系统可以在人类基因组中引入靶向插入、缺失和所有 12 种可能的碱基对碱基转换。自 2019 年首次发表关于 prime editing 的论文以来，世界各地的研究小组一直在研究这项有前途的技术，以开发针对遗传疾病的治疗方法。迄今为止，除囊性纤维化、β-地中海贫血、X 连锁严重联合免疫缺陷和癌症外，prime editing 已在肝脏、眼睛、皮肤、肌肉和神经退行性遗传性疾病的临床前研究中进行尝试。在这篇综述中，我们描述了我们目前在人类基因治疗中的 prime editing 进展，并概述了通过 prime editing 纠正致病突变的最佳策略。
