Modulating antibody N-glycosylation through feed additives using a multi-tiered approach

Kranjc, Jaka (avtor), Kramer, Lovro (avtor), Mikelj, Miha (avtor), Anderluh, Marko (avtor), Pišlar, Anja (avtor), Brinc, Matjaž (avtor)

Glycosylation of recombinant proteins is a post-translational modification that affects multiple physicochemical and biological properties of proteins. As such, it is a critical quality attribute that must be carefully controlled during protein production in the pharmaceutical industry. Glycosylation can be modulated by various conditions, including the composition of production media and feeds. In this study, the N-glycosylation-modulating effects of numerous compounds, including metal enzyme cofactors, enzyme inhibitors, and metabolic intermediates, were evaluated. Chinese hamster ovary cells producing three different IgG antibodies were cultivated in a fed-batch mode. First, a one-factor-at-a-time experiment was performed in 24-well deep well plates to identify the strongest modulators and appropriate concentration ranges. Then, a full response surface experiment was designed to gauge the effects and interactions of the 14 most effective hit compounds in an Ambr® 15 bioreactor system. A wide range of glycoform content was achieved, with an up to eight-fold increase in individual glycoforms compared to controls. The resulting model can be used to determine modulator combinations that will yield desired glycoforms in the final product.

• Jezik: Angleški jezik
• Ključne besede: bioprocess, glycosylation, modulators, modelling, Chinese hamster ovary, antibody production
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 13 str.
• Številčenje: Vol. 12, [article no.] 1448925
• PID: 20.500.12556/RUL-175589
• UDK: 577.112
• ISSN pri članku: 2296-4185
• DOI: 10.3389/fbioe.2024.1448925
• COBISS.SI-ID: 246929411
• Datum objave v RUL: 05.11.2025

Gradivo je del revije

• Naslov: Frontiers in bioengineering and biotechnology
• Skrajšan naslov: Front. bioeng. biotechnol.
• Založnik: Frontiers Editorial Office
• ISSN: 2296-4185
• COBISS.SI-ID: 523093017

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: bioprocesi, glikozilacija, modulatorji, modeliranje, jajčnik kitajskega hrčka, proizvodnja protiteles, rekombinantni protein

Projekti

• Financer: Drugi - Drug financer ali več financerjev
• Program financ.: Novartis Pharmaceutical Manufacturing LLC