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用于脊柱疼痛管理的CRISPR基因组编辑治疗应用进展

Advances in Therapeutic Applications of CRISPR Genome Editing for Spinal Pain Management.

作者信息

Kang Chan Young, Been Kyung Wook, Kang Myoung-Hee, Choi Myung Su, Kang Rae Hee, Hur Junseok W, Hur Junho K

机构信息

Department of Neurosurgery, College of Medicine, Korea University, Seoul, Korea.

Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea.

出版信息

Neurospine. 2025 Jun;22(2):421-440. doi: 10.14245/ns.2550462.231. Epub 2025 Jun 30.

Abstract

Neuropathic pain remains a significant clinical challenge due to the limited efficacy and sustainability of existing pharmacological treatments, underscoring the urgent need for mechanism-based therapeutic strategies. In recent years, gene-targeted interventions have emerged as promising modalities capable of modulating key molecular pathways implicated in chronic pain. Approaches such as antisense oligonucleotides and RNA interference have demonstrated encouraging preclinical results by selectively downregulating pain-associated genes. Based on these developments, genome-editing technologies-particularly the clustered regularly interspaced short palindromic repeats (CRISPR) system-have enabled more precise and long-lasting modifications at both the DNA and RNA levels. This review highlights how CRISPR-based approaches in addressing the critical issues of specificity and long-term efficacy in pain gene therapy and exploring the functional roles of key gene targets and regulatory elements. Although challenges such as off-target activity and immunogenic responses remain, growing preclinical evidence supports the feasibility of CRISPR-based approaches in neuropathic pain. Collectively, these developments position CRISPR as a transformative tool to innovate the standard care for persistent pain syndromes and contribute to broader biomedical and pharmaceutical developments through continued refinement of targeting strategies and safety profiles.

摘要

由于现有药物治疗的疗效和可持续性有限,神经性疼痛仍然是一个重大的临床挑战,这突出表明迫切需要基于机制的治疗策略。近年来,基因靶向干预已成为有前景的治疗方式,能够调节与慢性疼痛相关的关键分子途径。反义寡核苷酸和RNA干扰等方法通过选择性下调疼痛相关基因,已在临床前研究中取得了令人鼓舞的结果。基于这些进展,基因组编辑技术——特别是成簇规律间隔短回文重复序列(CRISPR)系统——已能够在DNA和RNA水平上实现更精确和持久的修饰。本综述重点介绍了基于CRISPR的方法如何解决疼痛基因治疗中的特异性和长期疗效等关键问题,以及如何探索关键基因靶点和调控元件的功能作用。尽管脱靶活性和免疫原性反应等挑战仍然存在,但越来越多的临床前证据支持基于CRISPR的方法在神经性疼痛治疗中的可行性。总体而言,这些进展使CRISPR成为一种变革性工具,可创新持续性疼痛综合征的标准治疗方法,并通过不断完善靶向策略和安全性概况,为更广泛的生物医学和制药发展做出贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fc9/12242737/308520d49ae8/ns-2550462-231f1.jpg

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