Abstract
Adenoviral vector (AdV) of the third generation also known as helper-dependent adenoviral vector (HDV) is an attractive delivery system for gene therapy applications. However, obtaining high quality-grade HDV in sufficient amount remains a challenge that hampers the extensive use of this vector in preclinical and clinical studies. Here we review recent progress in the large-scale manufacturing of HDV. The production of HDV is now amenable to large-scale volume with reduced process duration under optimized rescue and co-infection conditions. Also, efficient downstream processing of HDV with acceptable recovery of HDV and minimal contamination by the helper virus is described.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Altaras NE, Aunins JG, Evans RK, Kamen A, Konz JO, Wolf JJ. (2005) Production and formulation of adenovirus vectors Adv Biochem Eng Biotechnol 99, 193–260.
McConnell MJ, Imperiale MJ. (2004) Biology of adenovirus and its use as a vector for gene therapy Hum Gene Ther 15, 1022–33.
Tatsis N, Ertl HC. (2004) Adenoviruses as vaccine vectors Mol Ther 10, 616–29.
Dormond E, Perrier M, Kamen A. (2009) From the first to the third generation adenoviral vector: what parameters are governing the production yield? Biotechnol Adv 27, 133–44.
Graham FL, Smiley J, Russell WC, Nairn R. (1977) Characteristics of a human cell line transformed by DNA from human adenovirus type 5 J Gen Virol 36, 59–74.
Hardy S, Kitamura M, Harris-Stansil T, Dai Y, Phipps ML. (1997) Construction of adenovirus vectors through Cre-lox recombination J Virol 71, 1842–9.
Lieber A, He CY, Kirillova I, Kay MA. (1996) Recombinant adenoviruses with large deletions generated by Cre-mediated excision exhibit different biological properties compared with first-generation vectors in vitro and in vivo J Virol 70, 8944–60.
Parks RJ, Chen L, Anton M, Sankar U, Rudnicki MA, Graham FL. (1996) A helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal Proc Natl Acad Sci USA 93, 13565–70.
Ng P, Beauchamp C, Evelegh C, Parks R, Graham FL. (2001) Development of a FLP/frt system for generating helper-dependent adenoviral vectors Mol Ther 3, 809–15.
Umana P, Gerdes CA, Stone D, et al. (2001) Efficient FLPe recombinase enables scalable production of helper-dependent adenoviral vectors with negligible helper-virus contamination Nat Biotechnol 19, 582–5.
Oka K, Chan L. (2005) Construction and characterization of helper-dependent adenoviral vectors for sustained in vivo gene therapy Methods Mol Med 108, 329–50.
Dormond E, Meneses-Acosta A, Jacob D, et al. (2009) An efficient and scalable process for helper-dependent adenoviral vector production using polyethylenimine-adenofection Biotechnol Bioeng 102, 800–10.
Kumar-Singh R, Chamberlain JS. (1996) Encapsidated adenovirus minichromosomes allow delivery and expression of a 14 kb dystrophin cDNA to muscle cells Hum Mol Genet 5, 913–21.
Hartigan-O’Connor D, Barjot C, Crawford R, Chamberlain JS. (2002) Efficient rescue of gutted adenovirus genomes allows rapid production of concentrated stocks without negative selection Hum Gene Ther 13, 519–31.
Ng P, Parks RJ, Graham FL. (2002) Preparation of helper-dependent adenoviral vectors Methods Mol Med 69, 371–88.
Dormond E, Perrier M, Kamen A. (2009) Identification of critical infection parameters to control helper-dependent adenoviral vector production J Biotechnol 142, 142–50.
Dormond E, Chahal P, Bernier A, Tran R, Perrier M, Kamen A. (2009) An Efficient Process for the Purification of Helper-Dependent Adenoviral Vector and Removal of Helper Virus by Iodixanol Ultracentrifugation J Virol Methods (In press).
Côté J, Bourget L, Garnier A, Kamen A. (1997) Study of adenovirus production in serum-free 293SF suspension culture by GFP-expression monitoring Biotechnol Prog 13, 709–14.
Meneses-Acosta A, Dormond E, Jacob D, et al. (2008) Development of a suspension serum-free helper-dependent adenovirus production system and assessment of co-infection conditions J Virol Methods 148, 106–14.
Durocher Y, Perret S, Kamen A. (2002) High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells Nucleic Acids Res 30, E9.
O’Reilly DR, Miller LK, Luckow VA. Baculovirus Expression Vectors: A Laboratory Manual. New York: Oxford University Press; 1994.
Acknowledgements
Dr. V. Sandig and Dr. P. Lowenstein are also acknowledged for providing the authors with the HDV and the HV constructs. A. Bernier, N. Arcand, P.S. Chahal, D. Jacob, A. Meneses-Acosta,Y. Durocher, S. Perret, R. Tom, R. Gilbert, L. Bourget, and A. Migneault are acknowledged for their technical and scientific support.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC 2011
About this protocol
Cite this protocol
Dormond, E., Kamen, A.A. (2011). Manufacturing of Adenovirus Vectors: Production and Purification of Helper Dependent Adenovirus. In: Merten, OW., Al-Rubeai, M. (eds) Viral Vectors for Gene Therapy. Methods in Molecular Biology, vol 737. Humana Press. https://doi.org/10.1007/978-1-61779-095-9_6
Download citation
DOI: https://doi.org/10.1007/978-1-61779-095-9_6
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-094-2
Online ISBN: 978-1-61779-095-9
eBook Packages: Springer Protocols