Synthetic Biology: Emerging Concepts to Design and Advance Adeno-Associated Viral Vectors for Gene Therapy

Adv Sci (Weinh). 2021 Feb 26;8(9):2004018. doi: 10.1002/advs.202004018. eCollection 2021 May.


Three recent approvals and over 100 ongoing clinical trials make adeno-associated virus (AAV)-based vectors the leading gene delivery vehicles in gene therapy. Pharmaceutical companies are investing in this small and nonpathogenic gene shuttle to increase the therapeutic portfolios within the coming years. This prospect of marking a new era in gene therapy has fostered both investigations of the fundamental AAV biology as well as engineering studies to enhance delivery vehicles. Driven by the high clinical potential, a new generation of synthetic-biologically engineered AAV vectors is on the rise. Concepts from synthetic biology enable the control and fine-tuning of vector function at different stages of cellular transduction and gene expression. It is anticipated that the emerging field of synthetic-biologically engineered AAV vectors can shape future gene therapeutic approaches and thus the design of tomorrow's gene delivery vectors. This review describes and discusses the recent trends in capsid and vector genome engineering, with particular emphasis on synthetic-biological approaches.

Keywords: AAV; adeno‐associated virus; capsid modifications; engineering; gene delivery; molecular switches; vector design.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Dependovirus / genetics*
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics*
  • Synthetic Biology / methods*