Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.

IF 6.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Therapy. Nucleic Acids Pub Date : 2025-08-05 eCollection Date: 2025-09-09 DOI:10.1016/j.omtn.2025.102666

Mozhghan Raigani, Zohre Eftekhari, Ahmad Adeli, Fatemeh Kazemi-Lomedasht

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Abstract

Gene editing is a groundbreaking therapeutic approach that can potentially treat a broad spectrum of genetic and acquired diseases. This review highlights recent clinical trials employing advanced gene editing technologies such as CRISPR-Cas9, zinc-finger nucleases (ZFNs), and base editors across multiple disease areas including metabolic disorders, autoimmune diseases, muscular dystrophies, and inherited eye disorders. Central to the success of these therapies is the development of efficient and safe delivery systems, including lipid nanoparticles (LNPs), viral vectors (adenoviral and lentiviral), electroporation techniques, and virus-like particles (VLPs), which facilitate precise editing of target cells in vivo or ex vivo. These delivery platforms have enabled promising early-phase clinical trials demonstrating feasibility, safety, and durable gene modification in patient populations. For example, LNPs have been pivotal in delivering mRNA editors for liver-targeted metabolic diseases. At the same time, viral vectors have been used for ex vivo modification of T cells and hematopoietic stem cells in autoimmune and infectious diseases. Despite encouraging results, challenges remain in optimizing delivery specificity, minimizing off-target effects, and ensuring long-term safety and efficacy. Ongoing and upcoming trials continue to refine these delivery technologies and expand the therapeutic reach of gene editing.

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推进基因编辑治疗：跨多种疾病的临床试验和创新递送系统。

基因编辑是一种突破性的治疗方法，可以潜在地治疗广泛的遗传和获得性疾病。本综述重点介绍了最近使用先进基因编辑技术（如CRISPR-Cas9、锌指核酸酶（ZFNs）和碱基编辑器）在多种疾病领域（包括代谢紊乱、自身免疫性疾病、肌肉萎缩症和遗传性眼病）的临床试验。这些疗法成功的核心是开发高效和安全的递送系统，包括脂质纳米颗粒（LNPs）、病毒载体（腺病毒和慢病毒）、电穿孔技术和病毒样颗粒（VLPs），它们有助于在体内或体外精确编辑靶细胞。这些给药平台使早期临床试验证明了患者群体基因修饰的可行性、安全性和持久性。例如，LNPs在为肝脏靶向代谢疾病提供mRNA编辑器方面发挥了关键作用。同时，病毒载体已被用于自身免疫性疾病和感染性疾病的T细胞和造血干细胞的体外修饰。尽管取得了令人鼓舞的结果，但在优化给药特异性、最小化脱靶效应和确保长期安全性和有效性方面仍然存在挑战。正在进行和即将进行的试验将继续完善这些传递技术，并扩大基因编辑的治疗范围。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Therapy. Nucleic Acids MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

15.40

自引率

1.10%

发文量

336

审稿时长

20 weeks

期刊介绍： Molecular Therapy Nucleic Acids is an international, open-access journal that publishes high-quality research in nucleic-acid-based therapeutics to treat and correct genetic and acquired diseases. It is the official journal of the American Society of Gene & Cell Therapy and is built upon the success of Molecular Therapy. The journal focuses on gene- and oligonucleotide-based therapies and publishes peer-reviewed research, reviews, and commentaries. Its impact factor for 2022 is 8.8. The subject areas covered include the development of therapeutics based on nucleic acids and their derivatives, vector development for RNA-based therapeutics delivery, utilization of gene-modifying agents like Zn finger nucleases and triplex-forming oligonucleotides, pre-clinical target validation, safety and efficacy studies, and clinical trials.