Cell Culture and Upstream Processing

by Michael Butler (Editor)

Overview

Upstream processing refers to the production of proteins by cells genetically engineered to contain the human gene which will express the protein of interest. The demand for large quantities of specific proteins is increasing the pressure to boost cell culture productivity, and optimizing bioreactor output has become a primary concern for most pharmaceutical companies. Each chapter in Cell Culture and Upstream Processing is taken from presentations at the highly acclaimed IBC conferences as well as meetings of the European Society for Animal Cell Technology (ESACT) and Protein Expression in Animal Cells (PEACe) and describes how to improve yield and optimize the cell culture production process for biopharmaceuticals, by focusing on safety, quality, economics and operability and productivity issues.

Cell Culture and Upstream Processing will appeal to a wide scientific audience, both professional practitioners of animal cell technology as well as students of biochemical engineering or biotechnology in graduate or high level undergraduate courses at university.

Product Details

ISBN-13:	9781134148295
Publisher:	CRC Press
Publication date:	08/07/2007
Sold by:	Barnes & Noble
Format:	eBook
Pages:	204
File size:	2 MB

About the Author

Michael Butler-Associate Dean of Science; Professor of Cell Technology, Department of Microbiology, School of Science, University of Manitoba, Winnipeg, Canada

Table of Contents

1. Cell Line Development and Culture Strategies: Future Prospects to Improve Yields  2. Use of DNA Insulator Elements and Scaffold / Matrix-Attached Regions for Enhanced Recombinant Protein Expression  3. Targeted Gene Insertion to Enhance Protein Production From Cell Lines  4. Recombinant Human IgG Production From Myeloma and Chinese Hamster Ovary Cells  5. Cell Culture Media Development: Customization of Animal Origin-Free Components and Supplements  6. Post-Translational Modification of Recombinant Proteins  7. Metabolic Engineering to Control Glycosylation  8. An Alternative Approach: Humanization of N-glycosylation Pathways in Yeast  9. Perfusion or Fed-Batch? A Matter of Perspective

Editorial Reviews

Reviewer: Bruce A. Fenderson, PhD (Thomas Jefferson University)
Description: Today, over 40 licensed biopharmaceuticals are produced in bioreactors. These molecules include recombinant proteins, nucleic acid-based products, and monoclonal antibodies. Advances in our understanding of cellular metabolism and molecular biology have allowed improvements in bioreactor product-yield that now approach 5 grams/Liter. This book summarizes state-of-the art strategies for producing pharmaceuticals from cultured cells in nine chapters on topics ranging from use of DNA insulator elements and scaffold/matrix-attached regions for enhanced recombinant protein expression to humanization of N-glycosylation pathways in yeast. The experimental findings presented in this book were developed to maximize the yield of proteins in bioreactors and optimize protein function by manipulating glycosylation pathways. The primary focus of this book is on cell biology and biochemistry.
Purpose: According to the editor, the aim of this book is to share key developments with a wide audience. He writes, "It is hoped that this [book] will provide useful information for both scientific practitioners of animal cell technology as well as students of biochemical engineering." The authors are all prominent industrial and academic leaders in this field.
Audience: The book is written for basic science and clinical researchers, particularly those interested in biochemical engineering and biotechnology. Graduate students in these disciplines will appreciate this overview of current approaches to producing high-yield biopharmaceuticals. Readers will have to have good knowledge of cell biology and biochemistry
Features: This is not a protocol or methods book. Rather, the authors discuss innovative approaches to industrial-scale production of biological products. Major problems encountered using bioreactor systems are identified, and novel solutions are offered. For example, protein glycosylation affects protein stability and function, and so methods for manipulating O-linked and N-linked saccharide additions must be defined. Similarly, the transfection of cells is often complicated by the selective survival of low-expressing clones. To overcome the presumed negative position effects of randomly inserted DNAs, researchers are now using "chromatin borders" that protect transfected DNA against gene silencing. Each chapter provides an introduction, discussion of strategies that work, and interesting examples of results using black-and-white charts, tables, and gels. Each chapter includes an extensive list of references. The book is carefully edited and includes a helpful list of common abbreviations.
Assessment: Future applications of these technologies may revolutionize the pharmaceutical industry, allowing scientists to design "smart therapies" for devastating human diseases. This book highlights key issues in this field and provides a snapshot of successful approaches. I recommend it for all those interested in the use of bioreactors for product development.

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