Cell line development

Cori Gorman, Salina Arope, Mélanie Grandjean, Pierre-Alain Girod (auth.), Mohamed Al-Rubeai (eds.)9789048122448, 9048122449

Mammalian cell lines command an effective monopoly for the production of therapeutic proteins that require post-translational modifications. This unique advantage outweighs the costs associated with mammalian cell culture, which are far grater in terms of development time and manufacturing when compared to microbial culture. The development of cell lines has undergone several advances over the years, essentially to meet the requirement to cut the time and costs associated with using such a complex hosts as production platforms.

This book provides a comprehensive guide to the methodology involved in the development of cell lines and the cell engineering approach that can be employed to enhance productivity, improve cell function, glycosylation and secretion and control apoptosis. It presents an overall picture of the current topics central to expression engineering including such topics as epigenetics and the use of technologies to overcome positional dependent inactivation, the use of promoter and enhancer sequences for expression of various transgenes, site directed engineering of defined chromosomal sites, and examination of the role of eukaryotic nucleus as the controller of expression of genes that are introduced for production of a desired product. It includes a review of selection methods for high producers and an application developed by a major biopharmaceutical industry to expedite the cell line development process. The potential of cell engineering approch to enhance cell lines through the manipulation of single genes that play important roles in key metabolic and regulatory pathways is also explored throughout.

Table of contents :
Front Matter….Pages i-Viii
Use of MAR Elements to Increase the Production of Recombinant Proteins….Pages 1-32
Expression Engineering – The IE2 Promoter/Enhancer from Mouse CMV….Pages 33-52
Defeating Randomness – Targeted Integration as a Boost for Biotechnology….Pages 53-82
Importance of Genetic Environment for Recombinant Gene Expression….Pages 83-96
Expression Vector Engineering for Recombinant Protein Production….Pages 97-108
Cell Xpress™ Applications in Development and Characterization of Biopharmaceutical Recombinant Protein Producing Cell Lines….Pages 109-126
Selection Methods for High-Producing Mammalian Cell Lines….Pages 127-151
Engineering Mammalian Cells for Recombinant Monoclonal Antibody Production….Pages 153-173
Engineering Cell Function by RNA Interference….Pages 175-194
Apoptosis and Autophagy Cell Engineering….Pages 195-216
Glycoengineering and Modeling of Protein N-Glycosylation….Pages 217-231
Engineering the Secretory Pathway in Mammalian Cells….Pages 233-248
Back Matter….Pages 249-253