Date of Award

1-1-2015

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Nanoscale Science and Engineering

Program

Nanoscale Engineering

Content Description

1 online resource (ix, 98 pages) : color illustrations

Dissertation/Thesis Chair

Susan T Sharfstein

Committee Members

Nathaniel Cady, Steven Cramer, J.A. Melendez, Scott Tenenbaum

Keywords

Bioprocessing, Biotechnology, Monoclonal antibodies, Proteins, Transcription factors, Genetic transcription, Dwarf hamsters

Subject Categories

Biology | Nanoscience and Nanotechnology

Abstract

With the demand for monoclonal antibody (mAB) therapeutics continually increasing, the need to better understand what makes a high productivity clone has gained substantial interest. Monoclonal antibody producing Chinese hamster ovary (CHO) cells with different productivities were provided by a biopharmaceutical company for investigation. Gene copy numbers, mRNA levels, and mAb productivities were previously determined for two low producing clones and their amplified progeny. These results showed an increase in mRNA copy number in amplified clones, which correlated to the observed increases in specific productivity of these clones. The presence of multiple copies of mRNA per one copy of DNA in the higher productivity clones has been coined as transcriptional enhancement. The methylation status of the CMV promoter as well as transcription factor/promoter interactions were evaluated to determine the cause of transcriptional enhancement.

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