Cited by 66

Cellular pathways of recombinant adeno-associated virus production for gene therapy

Sha, Sha, Maloney, Andrew J., Katsikis, Georgios, Nguyen, Tam N.T., Neufeld, Caleb, Wolfrum, Jacqueline, Barone, Paul W., Springs, Stacy L. +3 more·2021·Biotechnology Advances

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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Crossref · 10.1016/j.biotechadv.2021.107764

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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].”

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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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