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中国医药导刊 ›› 2024, Vol. 26 ›› Issue (3): 224-230.

• 专栏:基因治疗 • 上一篇    下一篇

AAV基因治疗产品的免疫反应评估

何丹, 夏艳, 吴小兵*   

  1. 北京锦篮基因科技有限公司,北京 100176
  • 收稿日期:2024-01-04 出版日期:2024-03-28 发布日期:2024-03-28

Evaluation of Immune Response to AAV-Based Gene Therapy Products

  1. Genecradle Therapeutics Inc. Beijing 100176, China
  • Received:2024-01-04 Online:2024-03-28 Published:2024-03-28

摘要:

随着生命科学技术的进步,基因治疗因其特异性和精准性等优势已成为新药研发的重点领域。其中,腺相关病毒(adeno-associated virusAAV)载体是一种应用前景广阔的体内基因治疗载体,也是基因治疗产品载体研究的热点。目前,全球范围内已有7AAV相关的基因治疗产品获批上市,并有多项临床试验正在进行。AAV载体的免疫原性较低,但部分人群体内存在针对AAV的预存免疫,其进入体内后也会诱导机体产生先天免疫反应,随后可能触发针对AAV衣壳和转基因产物的适应性免疫反应,从而影响药物的有效性和安全性。本综述旨在概述AAV基因治疗引起的免疫反应特征,并简要总结在临床前和临床研究中对AAV基因治疗免疫反应的评估,以期为AAV基因治疗药物评价提供参考。

关键词: 腺相关病毒载体, AAV, 基因治疗, 免疫反应评估

Abstract:

With the advancement of life science technologies gene therapy has emerged as a focal point in new drug development due to its specificity and precision. Among various vectors adeno-associated virus AAV has gained prominence as an intracellular gene therapy vector standing out as a hot research focus for gene therapy products. Currently seven AAV-based gene therapy products have received regulatory approval and entered the market worldwide and several clinical trials are underway. AAV vectors exhibit low immunogenicity however pre-existing immunity against AAV in certain populations may induce innate immune responses upon vector administration. Subsequently this may trigger adaptive immune reactions against the AAV capsid and transgene products potentially influencing the efficacy and safety of the therapeutic intervention. This review aims to outline the characteristics of immune responses induced by AAV-based gene therapy and briefly summarize the evaluation of immune response to AAV-based gene therapy in preclinical and clinical studies. The objective is to provide a reference for the evaluation of AAV-based gene therapy products.


Key words: Adeno-associated virus vector , AAV , Gene therapy , Evaluation of immune response

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