Application of synthetic biology in AAV gene therapy

WU Xin; YE Haifeng

doi:10.12405/j.issn.2097-1486.2024.01.004

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Application of synthetic biology in AAV gene therapy

更新时间：2024-08-15

- Application of synthetic biology in AAV gene therapy
- Emerging Science and Technology(Nat.Sci.Ed.) Vol. 3, Issue 1, Pages: 25-38(2024)
- 作者机构：
  
  1.华东师范大学生命科学学院上海市调控生物学重点实验室，上海 200241
  2.山西医科大学医学技术研究院，山西太原 030006
- 作者简介：
- 基金信息：
- DOI：10.12405/j.issn.2097-1486.2024.01.004
  CLC： Q812
- Published：15 March 2024，
  
  Received：11 January 2024，
  
  Revised：20 February 2024，
- 稿件说明：
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武鑫,叶海峰.合成生物学在AAV基因治疗中的应用[J].新兴科学和技术趋势,2024,3(1):25-38.

WU Xin,YE Haifeng.Application of synthetic biology in AAV gene therapy[J].Emerging Science and Technology,2024,3(1):25-38.
武鑫,叶海峰.合成生物学在AAV基因治疗中的应用[J].新兴科学和技术趋势,2024,3(1):25-38. DOI： 10.12405/j.issn.2097-1486.2024.01.004.

WU Xin,YE Haifeng.Application of synthetic biology in AAV gene therapy[J].Emerging Science and Technology,2024,3(1):25-38. DOI： 10.12405/j.issn.2097-1486.2024.01.004.

摘要

基因治疗在精准医学中崭露头角，对医疗和诊断产生深远影响。腺相关病毒（AAV）基因载体成为基因治疗中领先的基因传递工具，其作为安全、免疫原性低、血清型多样、具有组织特异性的临床基因治疗载体，在体内具有长期效果。然而，AAV递送的基因过量表达可能引起毒性或副作用。因此，新一代合成生物学工程化的AAV载体正在崛起，合成生物学能够在细胞转导和基因表达的不同阶段对载体功能进行控制，精准调控目的基因表达。本文将围绕基因环路的设计思路和方法，AAV基因治疗的研究进展以及合成生物学在AAV基因治疗方面的研究进展进行介绍。最后对合成生物学驱动的AAV基因治疗走向临床治疗的应用前景和挑战进行展望。合成生物学驱动的AAV基因治疗在提供精准和个性化治疗方案方面展现出巨大潜力，有望扩大治疗范围并降低成本，但同时面临免疫应答、靶向性、生产成本及伦理监管等关键挑战。

Abstract

The emergence of gene therapy in precision medicine has made a profound impact on healthcare and diagnostics. As leading gene delivery tools in gene therapy， adeno-associated virus （AAV） gene vectors are clinically approved carriers， ensuring safety， low immunogenicity， diverse serotypes， tissue specificity， and long-term effectiveness in vivo. However， gene over-expression delivered by AAV may lead to toxicity or side effects. Consequently， new AAV vectors engineered through synthetic biology are on the rise. Synthetic biology can control the function of carriers at different stages of cellular transduction and gene expression， thus precisely controlling target gene expression. This article focuses on the design principles and methods of gene circuits， advancements in AAV gene therapy research， and progress in synthetic biology within the context of AAV gene therapy. It provides insights into the prospective clinical applications and the challenges of AAV gene therapy driven by synthetic biology. Synthetic biology-driven AAV gene therapy has exhibited substantial potential in providing precise and personalized treatment solutions， with the promise of expanding the therapeutic scope and reducing costs. However， it also faces key challenges， including immune responses， targeting specificity， production costs， and stringent ethical and regulatory considerations.

关键词

合成生物学腺相关病毒AAV基因治疗基因环路

Keywords

synthetic biologyadeno-associated virusgene therapygene circuits

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