AAV- based vector improvements unrelated to capsid protein modification

Ekaterina M Shitik; Igor K Shalik; Dmitry V Yudkin

doi:10.3389/fmed.2023.1106085

AAV- based vector improvements unrelated to capsid protein modification

Front Med (Lausanne). 2023 Feb 3:10:1106085. doi: 10.3389/fmed.2023.1106085. eCollection 2023.

Authors

Ekaterina M Shitik¹, Igor K Shalik¹, Dmitry V Yudkin¹

Affiliation

¹ Federal Scientific and Technical Program on the Development of Genetic Technologies, State Research Center of Virology and Biotechnology "Vector", Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Kol'tsovo, Russia.

Abstract

Recombinant adeno-associated virus (rAAV) is the leading platform for delivering genetic constructs in vivo. To date, three AAV-based gene therapeutic agents have been approved by the FDA and are used in clinical practice. Despite the distinct advantages of gene therapy development, it is clear that AAV vectors need to be improved. Enhancements in viral vectors are mainly associated with capsid protein modifications. However, there are other structures that significantly affect the AAV life cycle and transduction. The Rep proteins, in combination with inverted terminal repeats (ITRs), determine viral genome replication, encapsidation, etc. Moreover, transgene cassette expression in recombinant variants is directly related to AAV production and transduction efficiency. This review discusses the ways to improve AAV vectors by modifying ITRs, a transgene cassette, and the Rep proteins.

Keywords: Rep proteins; a transgene cassette; adeno-associated virus; gene therapy; inverted terminal repeats.

Publication types

Review

Grants and funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement #075-15-2019-1665).