Therapeutic in vivo genome editing: innovations and challenges in rAAV vector-based CRISPR delivery

IF 5.9 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy Pub Date : 2025-11-12 DOI:10.1038/s41434-025-00573-2

Jin-Seok Gil, Soyeon Lee, Taeyoung Koo

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Abstract

The integration of CRISPR systems with recombinant adeno-associated virus (rAAV) vectors has opened new possibilities for therapeutic genome editing, offering potential treatments for both genetic and non-genetic disorders. rAAV vectors have emerged as promising vehicles for in vivo gene therapy due to their favorable safety profile, high tissue specificity, and ability to induce sustained transgene expression. However, their limited packaging capacity has been a significant challenge for delivering large CRISPR molecules. To overcome this limitation, innovative strategies have been developed, including the use of compact Cas orthologs, dual rAAV vector systems, and trans-splicing rAAV vectors. These approaches have significantly improved the efficiency of genome editing for therapeutic applications. This review presents recent advancements in rAAV-CRISPR-mediated in vivo gene therapy, highlighting key technological innovations, current challenges, and the therapeutic potential of these strategies in the development of next-generation gene therapies.

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治疗性体内基因组编辑：基于rAAV载体的CRISPR传递的创新和挑战。

CRISPR系统与重组腺相关病毒（rAAV）载体的整合为治疗性基因组编辑开辟了新的可能性，为遗传性和非遗传性疾病提供了潜在的治疗方法。由于其良好的安全性、高组织特异性和诱导持续转基因表达的能力，rAAV载体已成为体内基因治疗的有前途的载体。然而，它们有限的包装能力一直是递送大型CRISPR分子的重大挑战。为了克服这一限制，已经开发了创新的策略，包括使用紧凑的Cas同源物，双rAAV载体系统和反式剪接rAAV载体。这些方法显著提高了基因组编辑在治疗应用中的效率。本文综述了raav - crispr介导的体内基因治疗的最新进展，重点介绍了关键技术创新、当前挑战以及这些策略在下一代基因治疗开发中的治疗潜力。

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

Gene Therapy 医学-生化与分子生物学

CiteScore

9.70

自引率

2.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Gene Therapy covers both the research and clinical applications of novel therapeutic techniques based on a genetic component. Over the last few decades, significant advances in technologies ranging from identifying novel genetic targets that cause disease through to clinical studies, which show therapeutic benefit, have elevated this multidisciplinary field to the forefront of modern medicine.