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.
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