Cellular pathways of recombinant adeno-associated virus production for gene therapy
Abstract
Recombinant adeno-associated viruses (rAAVs) are among the most important vectors for in vivo gene therapies. With the rapid development of gene therapy, current rAAV manufacturing capacity faces a challenge to meet the emerging demand for these therapies in the future. To examine the bottlenecks in rAAV production during cell culture, we focus here on an analysis of cellular pathways of rAAV production, based on an overview of assembly mechanisms first in the wild-type (wt) AAV replication and then in the common methods of rAAV production. The differences analyzed between the wild-type and recombinant systems provide insights into the mechanistic differences that may correlate with viral productivity. Based on these analyses, we identify potential barriers to high productivity of rAAV and discuss future directions for improvement to meet the emerging needs set by the growth of rAAV-based therapy and the needs of patients.
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No unified mechanistic framework currently captures AdV, AAV, and LV processes within the same HEK293 host using a consistent mathematical structure that allows cross platform parameterization with minimal structural modification.
“Despite these contributions, no unified mechanistic framework currently captures AdV, AAV, and LV processes within the same HEK293 host using a consistent mathematical structure that allows cross platform parameterization with minimal structural modification [21, 22].”
From Mechanistic model for HEK293 viral vector processes and its application in a digital shadow framework (2026) · cites this paper as [21]
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AAV vectors applied to the treatment of CNS disorders: Clinical status and challenges
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- Authors
- Sha, S., Maloney, A. J., Katsikis, G., Nguyen, T. N. T., Neufeld, C., Wolfrum, J., Barone, P. W., Springs, S. L., Manalis, S. R., Sinskey, A. J., & Braatz, R. D.
- Venue
- Biotechnology Advances
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 49
- Pages
- 107764
- ISSN
- 0734-9750
- Cited by
- 66
- References
- 14
- Language
- en
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