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Essentially Leading Antibody Production: An Investigation of Amino Acids, Myeloma, and Natural V-Region Signal Peptides in Producing Pertuzumab and Trastuzumab Variants

Lookup NU author(s): Dr Alex Ling, Dr Yuen Ling Ng, Professor Anil Wipat

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© Copyright © 2020 Ling, Su, Lua, Poh, Ng, Wipat and Gan.Boosting the production of recombinant therapeutic antibodies is crucial in both academic and industry settings. In this work, we investigated the usage of varying signal peptides by antibody V-genes and their roles in recombinant transient production, systematically comparing myeloma and the native signal peptides of both heavy and light chains in 168 antibody permutation variants. We found that amino acids count and types (essential or non-essential) were important factors in a logistic regression equation model for predicting transient co-transfection protein production rates. Deeper analysis revealed that the culture media were often incomplete and that the supplementation of essential amino acids can improve the recombinant protein yield. While these findings are derived from transient HEK293 expression, they also provide insights to the usage of the large repertoire of antibody signal peptides, where by varying the number of specific amino acids in the signal peptides attached to the variable regions, bottlenecks in amino acid availability can be mitigated.


Publication metadata

Author(s): Ling W-L, Su CT-T, Lua W-H, Poh J-J, Ng Y-L, Wipat A, Gan SK-E

Publication type: Article

Publication status: Published

Journal: Frontiers in Immunology

Year: 2020

Volume: 11

Print publication date: 01/12/2020

Online publication date: 07/12/2020

Acceptance date: 05/11/2020

Date deposited: 03/02/2021

ISSN (electronic): 1664-3224

Publisher: Frontiers Media S.A.

URL: https://doi.org/10.3389/fimmu.2020.604318

DOI: 10.3389/fimmu.2020.604318


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