ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Cell and Gene Therapy
Altering VP1 and VP2 expression in trans affects the transduction efficiency of AAV9
Provisionally accepted
Maxim K. Efremov*
Alima Galieva
Andrew Brovin
Natalia V. MesonzhnikMikhail B. Afonin
Elena N Subcheva
Alexander Karabelsky- Sirius University, Sochi, Russia
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Currently, adeno-associated virus (AAV) is one of the most reliable carrier for gene delivery in both proliferating and non-proliferating cells. Stable and long-lasting transgene expression has made this viral vector a key platform for the development of advanced therapy. Nevertheless, the widespread clinical use of AAV-based drugs remains limited due to their immunogenicity, low capsid capacity, and restricted tissue tropism. Tissue tropism depends largely on the efficiency of the transduction efficiency of AAV capsids. In this study, we modified the standard three-plasmid transfection protocol to provide independent expression of VP1 or VP2 proteins from separate plasmids. Adjusting the ratio of these plasmids in the transfection mixture enabled alteration of the stoichiometric composition of the capsids, as SDS-PAGE and mass spectrometry confirmed. Increasing the amount of VP1 or VP2 in the capsid composition enhanced transduction efficiency, as demonstrated in vitro experiments on HEK293 cells. Obtained results contribute to a more comprehensive understanding of the AAV biology and have perspective of application in gene therapy.
Keywords: aav, adeno-associated virus, capsid engineering, capsidstoichiometry, Gene Therapy, Transduction efficiency
Received: 24 Nov 2025; Accepted: 31 Jan 2026.
Copyright: © 2026 Efremov, Galieva, Brovin, Mesonzhnik, Afonin, Subcheva and Karabelsky. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Maxim K. Efremov
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