title: Influence of HEK293 metabolism on the production of viral vectors and vaccine.
abstract: Mammalian cell cultures are increasingly used for the production of complex biopharmaceuticals including viral vectors and vaccines. HEK293 is the predominant cell line used for the transient expression of recombinant proteins and a well-established system for the production of viral vectors. Understanding metabolic requirements for high productivity in HEK293 cells remains an important area of investigation. Many authors have presented approaches for increased productivity through optimization of cellular metabolism from two distinct perspectives. One is a non-targeted approach, which is directed to improving feeding strategies by addition of exhausted or critical substrates and eventually removal of toxic metabolites. Alternatively, a targeted approach has attempted to identify specific targets for optimization through better understanding of the cellular metabolism under different operating conditions. This review will present both approaches and their successes with regards to improvement of viral production in HEK293 cells outlining the key relations between HEK293 cell metabolism and viral vector productivity. Also, we will summarize the current knowledge on HEK293 metabolism indicating remaining issues to address and problems to resolve to maximize the productivity of viral vectors in HEK293 cells.
authors.affiliation: Laboratoire Virologie et Pathologie Humaine (VirPath), EA4610 Université Claude Bernard Lyon 1, 7 rue guillaume paradin, 69008 Lyon, France.
authors.forename: Emma
authors.initials: E
authors.lastname: Petiot
authors.affiliation: Vaccine Program National Research Council, 6100 Royalmount Ave, Montreal, QC, Canada H4P 2R2.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Cuperlovic-Culf
authors.affiliation: Vaccine Program National Research Council, 6100 Royalmount Ave, Montreal, QC, Canada H4P 2R2.
authors.forename: Chun Fang
authors.initials: CF
authors.lastname: Shen
authors.affiliation: Vaccine Program National Research Council, 6100 Royalmount Ave, Montreal, QC, Canada H4P 2R2; Bioengineering Dpt., McGill University, 817, Sherbrooke West, Montreal, QC, Canada H3A 0C3. Electronic address: amine.kamen@mcgill.ca.
authors.forename: Amine
authors.initials: A
authors.lastname: Kamen
mesh_terms: D018929:Cell Culture Techniques; D002460:Cell Line; D004337:Drug Carriers / Q000302:isolation & purification* / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D013678:Technology, Pharmaceutical; D014612:Vaccines / Q000302:isolation & purification* / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D014612:Vaccines
keywords: HEK293 cell metabolism; Metabolomics; Viral production processes; Viral vector and vaccine