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Biotechnol. Adv., Feb 07 2024, S0734-9750(24)00016-8 | https://doi.org/10.1016/j.biotechadv.2024.108322
Decoding cellular mechanism of recombinant adeno-associated virus (rAAV) and engineering host-cell factories toward intensified viral vector manufacturing
Yongdan Wang a,1, Qiang Fu b,1, So Young Park c, Yong Suk Lee c, Seo-Young Park d, Dong-Yup Lee d, Seongkyu Yoon a
aDepartment of Chemical Engineering, University of Massachusetts Lowell, Lowell, MA 01854, United States of America
bDepartment of Biomedical Engineering and Biotechnology, University of Massachusetts Lowell, Lowell, MA 01854, United States of America
cDepartment of Pharmaceutical Sciences, University of Massachusetts Lowell, Lowell, MA 01854, United States of America
dSchool of Chemical Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea
1Wang and Fu equally contributed to this paper.
Corresponding author : Seongkyu Yoon
Abstract
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.
논문정보
- Review Paper
- 2024년 02월 (BRIC 등록일 2024-02-20)
- 국내+국외 연구진
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