Cell Line Development

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

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Cell Engineering Volume 6 Series Editor Professor Mohamed Al-Rubeai UCD School of Chemical and Bioprocess Engineering University College Dublin Dublin, Ireland

Editorial Board Dr Hansjorg Hauser Helmholtz Centre for Infection Research Braunschweig Germany Professor Michael Betenbaugh Johns Hopkins University Baltimore, USA Professor Martin Fussenegger Swiss Federal Institute of Technology Zurich, Switzerland Professor. Nigel Jenkins National Institute for Bioprocessing Research and Training Dublin, Ireland Dr Otto-Wilhelm Merten A.F.M.-Genethon 11 Gene Therapy Program Evry, France

For other titles published in this series, go to www.springer.com/series/5728

CELL ENGINEERING Vol. 6: Cell Line Development

Edited by

Mohamed Al-Rubeai University College Dublin, Ireland

Editor Prof. Dr. Mohamed Al-Rubeai School of Chemical and Bioprocess Engineering University College Dublin Belfield, Dublin 4 Ireland

ISBN 978-90-481-2244-8 e-ISBN 978-90-481-2245-5 DOI 10.1007/978-90-481-2245-5 Springer Dordrecht Heidelberg London New York Library of Congress Control Number: 2009929356 © Springer Science+Business Media B.V. 2009 No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission from the Publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

Cell Engineering – Overview

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 complex hosts as production platforms. This book reviews the aspects involved in the development of cell lines and the cell engineering approach that can be employed to enhance productivity, improve cellular metabolism, control proliferation and apoptosis, and reduce instability. Cell engineering is a new research approach which began in the early 1990s, coinciding with an increasing interest in apoptosis. This approach of manipulation of apoptotic regulatory functions in cells was highlighted in an article appearing in 1995 in “Trends in Biotechnology”, in which we suggested that through the manipulation of cell lines by transfecting them with anti-apoptotic genes, one may be able to enhance the robustness and survival of those cells in culture. Since then several papers have been published which demonstrate the effectiveness of this approach; this has since evolved to embrace methodologies offered by molecular biology for the development of cell lines, which could provide platforms to improve recombinant protein production and the efficiency of industrial culture processes. The underlying principles of cell engineering are very simple, essentially involving the identification of a gene of interest, expression