Date of Award

8-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Chair/Advisor

Dr. Sarah Harcum

Committee Member

Dr. Christopher Saski

Committee Member

Dr. Kimberly Paul

Committee Member

Dr. Dan Simionescu

Committee Member

Dr. Angela Alexander-Bryant

Abstract

Recombinant protein therapeutics have become integral in the treatment and prevention of an increasingly broad range of diseases and conditions. The vast majority of these biopharmaceuticals are produced in Chinese hamster ovary (CHO) cells due to their well-established expression systems, scalability, and ability to produce safe, human-compatible glycoproteins. Previous research has aimed to increase productivity while maintaining or improving product quality metrics, resulting in substantial improvements in product yields over the past forty years. This progress has been largely driven by 'omics and multivariate approaches, which offer valuable mechanistic insights and identify process bottlenecks.

Within this dissertation, CHO cell stress responses to ammonia, serum-free medium adaptation, temperature reduction, low pH, low basal glucose concentrations, and oxidative stress were analyzed for impacts to culture outcomes through transcriptomic and/or metabolic analysis. Several biomarkers and potential engineering targets were identified which could be leveraged to improve process outcomes such as productivity and product quality. The data from these studies could further be used to improve production processes through cell line engineering and media development.

Available for download on Sunday, August 31, 2025

Share

COinS