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  4. Scalable Production of AAV Vectors in Orbitally Shaken HEK293 Cells
 
research article

Scalable Production of AAV Vectors in Orbitally Shaken HEK293 Cells

Blessing, Daniel
•
Vachey, Gabriel
•
Pythoud, Catherine
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June 14, 2019
Molecular Therapy-Methods & Clinical Development

Adeno-associated virus (AAV) vectors are currently among the most commonly applied for in vivo gene therapy approaches. The evaluation of vectors during clinical development requires the production of considerable amounts of highly pure and potent vectors. Here, we set up a scalable process for AAV production, using orbitally shaken bioreactors and a fully characterized suspension-adapted cell line, HEKExpress. We conducted a proof-of-concept production of AAV2/8 and AAV2/9 vectors using HEKExpress cells. Furthermore, we compared the production of AAV2/9 vectors using this suspension cell line to classical protocols based on adherent HEK293 cells to demonstrate bioequivalence in vitro and in vivo. Following upstream processing, we purified vectors via gradient centrifugation and immunoaffinity chromatography. The in vitro characterization revealed differences due to the purification method, as well as the transfection protocol and the corresponding HEK293 cell line. The purification method and cell line used also affected in vivo transduction efficiency after bilateral injection of AAV2/9 vectors expressing a GFP reporter fused with a nuclear localization signal (AAV2/9-CBA-nlsGFP) into the striatum of adult mice. These results show that AAV vectors deriving from suspension HEKExpress cells are bioequivalent and may exhibit higher potency than vectors produced with adherent HEK293 cells.

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Type
research article
DOI
10.1016/j.omtm.2018.11.004
Web of Science ID

WOS:000471284200002

Author(s)
Blessing, Daniel
Vachey, Gabriel
Pythoud, Catherine
Rey, Maria
Padrun, Vivianne  
Wurm, Florian M.  
Schneider, Bernard L.  
Deglon, Nicole  
Date Issued

2019-06-14

Published in
Molecular Therapy-Methods & Clinical Development
Volume

13

Start page

14

End page

26

Subjects

Medicine, Research & Experimental

•

Research & Experimental Medicine

•

recombinant-adenoassociated-virus

•

serum-free production

•

gene-transfer

•

transient transfection

•

mammalian-cells

•

viral vectors

•

serotype 8

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high-titer

•

purification

•

expression

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
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LBTC  
PTBTG  
Available on Infoscience
June 28, 2019
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/158621
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