Protein and Genome Evolution in Mammalian Cells for Biotechnology Applications |
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Authors: | Brian S Majors Gisela G Chiang Michael J Betenbaugh |
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Institution: | (1) Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, 221 Maryland Hall, Baltimore, MD 21218-2694, USA;(2) Cellular Engineering, Biogen Idec, Inc., 14 Cambridge Center, Cambridge, MA 02142, USA;(3) Present address: Cellular Engineering, Biogen Idec, Inc., 14 Cambridge Center, Cambridge, MA 02142, USA |
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Abstract: | Mutation and selection are the essential steps of evolution. Researchers have long used in vitro mutagenesis, expression,
and selection techniques in laboratory bacteria and yeast cultures to evolve proteins with new properties, termed directed
evolution. Unfortunately, the nature of mammalian cells makes applying these mutagenesis and whole-organism evolution techniques
to mammalian protein expression systems laborious and time consuming. Mammalian evolution systems would be useful to test
unique mammalian cell proteins and protein characteristics, such as complex glycosylation. Protein evolution in mammalian
cells would allow for generation of novel diagnostic tools and designer polypeptides that can only be tested in a mammalian
expression system. Recent advances have shown that mammalian cells of the immune system can be utilized to evolve transgenes
during their natural mutagenesis processes, thus creating proteins with unique properties, such as fluorescence. On a more
global level, researchers have shown that mutation systems that affect the entire genome of a mammalian cell can give rise
to cells with unique phenotypes suitable for commercial processes. This review examines the advances in mammalian cell and
protein evolution and the application of this work toward advances in commercial mammalian cell biotechnology. |
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Keywords: | Directed evolution Protein engineering Mammalian cell culture Somatic hypermutation Cellular engineering |
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