Journal
ISCIENCE
Volume 26, Issue 4, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2023.106487
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In this study, a tetracycline-dependent promoter was used to regulate the expression of capsids in AAV production system, resulting in increased viral yield and decreased empty capsids in different serotypes without affecting the infectivity of AAV vectors in vitro and in vivo. The change in replicase expression pattern improved the quantity and quality of the AAV vectors, while the control of capsid expression timing reduced the presence of empty capsids. These findings provide new insights for the development of AAV vector production systems in gene therapy.
Adeno-associated virus (AAV) vectors are promising tools for gene therapy. The current AAV vector system produces an abundance of empty capsids that are eliminated before clinical use, leading to increased costs for gene therapy. In the present study, we established an AAV production system that regulates the timing of capsid expression using a tetracycline-dependent promoter. Tetracycline-regulating capsid expression increased viral yield and reduced empty capsids in various serotypes without altering AAV vector infectivity in vitro and in vivo. The replicase expression pattern change observed in the developed AAV vector system improved viral quantity and quality, whereas timing control of capsid expression reduced empty capsids. These findings provide a new perspective on the development of AAV vector production systems in gene therapy.
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