Decoding cellular mechanism of recombinant adeno-associated virus (rAAV) and engineering host-cell factories toward intensified viral vector manufacturing
Copyright © 2024 Elsevier Inc. All rights reserved..
Recombinant adeno-associated virus (rAAV) is one of the prominent gene delivery vehicles that has opened promising opportunities for novel gene therapeutic approaches. However, the current major viral vector production platform, triple transfection in mammalian cells, may not meet the increasing demand. Thus, it is highly required to understand production bottlenecks from the host cell perspective and engineer the cells to be more favorable and tolerant to viral vector production, thereby effectively enhancing rAAV manufacturing. In this review, we provided a comprehensive exploration of the intricate cellular process involved in rAAV production, encompassing various stages such as plasmid entry to the cytoplasm, plasmid trafficking and nuclear delivery, rAAV structural/non-structural protein expression, viral capsid assembly, genome replication, genome packaging, and rAAV release/secretion. The knowledge in the fundamental biology of host cells supporting viral replication as manufacturing factories or exhibiting defending behaviors against viral production is summarized for each stage. The control strategies from the perspectives of host cell and materials (e.g., AAV plasmids) are proposed as our insights based on the characterization of molecular features and our existing knowledge of the AAV viral life cycle, rAAV and other viral vector production in the Human embryonic kidney (HEK) cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:71 |
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| Enthalten in: |
Biotechnology advances - 71(2024) vom: 07. März, Seite 108322 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Yongdan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biotechadv.2024.108322 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a Recombinant adeno-associated virus (rAAV) is one of the prominent gene delivery vehicles that has opened promising opportunities for novel gene therapeutic approaches. However, the current major viral vector production platform, triple transfection in mammalian cells, may not meet the increasing demand. Thus, it is highly required to understand production bottlenecks from the host cell perspective and engineer the cells to be more favorable and tolerant to viral vector production, thereby effectively enhancing rAAV manufacturing. In this review, we provided a comprehensive exploration of the intricate cellular process involved in rAAV production, encompassing various stages such as plasmid entry to the cytoplasm, plasmid trafficking and nuclear delivery, rAAV structural/non-structural protein expression, viral capsid assembly, genome replication, genome packaging, and rAAV release/secretion. The knowledge in the fundamental biology of host cells supporting viral replication as manufacturing factories or exhibiting defending behaviors against viral production is summarized for each stage. The control strategies from the perspectives of host cell and materials (e.g., AAV plasmids) are proposed as our insights based on the characterization of molecular features and our existing knowledge of the AAV viral life cycle, rAAV and other viral vector production in the Human embryonic kidney (HEK) cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Capsid assembly and genome packaging | |
| 650 | 4 | |a Cell line engineering | |
| 650 | 4 | |a Gene therapy | |
| 650 | 4 | |a Genome replication | |
| 650 | 4 | |a Host cell responses and factors | |
| 650 | 4 | |a Mammalian host cell factory | |
| 650 | 4 | |a Plasmid trafficking and nuclear entry | |
| 650 | 4 | |a Protein synthesis | |
| 650 | 4 | |a rAAV production | |
| 650 | 4 | |a rAAV release/secretion | |
| 700 | 1 | |a Fu, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Park, So Young |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Yong Suk |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Seo-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Dong-Yup |e verfasserin |4 aut | |
| 700 | 1 | |a Yoon, Seongkyu |e verfasserin |4 aut | |
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