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Journal ArticleDOI

Selection methods for high-producing mammalian cell lines.

01 Sep 2007-Trends in Biotechnology (Springer, Dordrecht)-Vol. 25, Iss: 9, pp 425-432
TL;DR: There is an increasing need for methods for the selection of mammalian cell lines stably expressing recombinant products at high levels in an efficient, cost-effective and high-throughput manner.
About: This article is published in Trends in Biotechnology.The article was published on 2007-09-01. It has received 229 citations till now.
Citations
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Journal ArticleDOI
TL;DR: Over the past four years, several new types of experimental biologic treatment have received commercial registration, but the emergence of biosimilars represents the biggest shift in the biologic approval landscape.
Abstract: Over the past four years, several new types of experimental biologic treatment have received commercial registration, but the emergence of biosimilars represents the biggest shift in the biologic approval landscape.

890 citations

Journal ArticleDOI
TL;DR: This review seeks to highlight the advantages of this technique in microbial fermentations monitoring and control, as well as in the development of more accurate kinetic models directed to bioprocesses optimization.

277 citations

Journal ArticleDOI
TL;DR: In this paper, the authors reviewed established advances in protein expression and clone screening, which are the core technologies in mammalian cell line development, and proposed to improve the speed and efficiency of generating robust and highly productive cell line for large scale production of protein therapeutics.
Abstract: From 2006 to 2011, an average of 15 novel recombinant protein therapeutics have been approved by US Food and Drug Administration (FDA) annually. In addition, the expiration of blockbuster biologics has also spurred the emergence of biosimilars. The increasing numbers of innovator biologic products and biosimilars have thus fuelled the demand of production cell lines with high productivity. Currently, mammalian cell line development technologies used by most biopharmaceutical companies are based on either the methotrexate (MTX) amplification technology or the glutamine synthetase (GS) system. With both systems, the cell clones obtained are highly heterogeneous, as a result of random genome integration by the gene of interest and the gene amplification process. Consequently, large numbers of cell clones have to be screened to identify rare stable high producer cell clones. As such, the cell line development process typically requires 6 to 12 months and is a time, capital and labour intensive process. This article reviews established advances in protein expression and clone screening which are the core technologies in mammalian cell line development. Advancements in these component technologies are vital to improve the speed and efficiency of generating robust and highly productive cell line for large scale production of protein therapeutics.

263 citations


Cites background from "Selection methods for high-producin..."

  • ...Furthermore, high producing clones are typically rare in a population of transfected cells because the active region supporting high gene expression in the chromosome is rare [10] and these high producer cell clones typically have lower growth rates since a significant portion of resources are being used for expression of the recombinant protein [97]....

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  • ...Nevertheless, it has been reported that the laser used in LEAP TM may damage high producing cell clone [10]....

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Journal ArticleDOI
TL;DR: The growing interest in biosimilar antibodies as affordable versions of therapeutic antibodies may provide alternative treatment options as well potentially decreasing costs and regulatory authorities continue to refine the requirements for demonstrating quality, efficacy and safety of biosimilar compared to originator products.

222 citations


Cites methods from "Selection methods for high-producin..."

  • ...Several strategies have since evolved from the limiting dilution approach that utilise automated cell sorting equipment [151,152]....

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Journal ArticleDOI
TL;DR: This review will discuss the cell encapsulation process, the immunogenicity of the encapsulating hydrogel, the Immunity, the transport properties of the hydrogels, and thehydrogel mechanical properties, and will propose new strategies to improve theHydrogel and cell interaction for successful cell-based drug delivery strategies.
Abstract: Stem cells, progenitor cells, and lineage-committed cells are being considered as a new generation of drug depots for the sustained release of therapeutic biomolecules Hydrogels are often used in conjunction with the therapeutic secreting cells to provide a physical barrier to protect the cells from hostile extrinsic factors Although the hydrogels significantly improve the therapeutic efficacy of transplanted cells, there have been no successful products commercialized based on these technologies Recently, biomaterials are increasingly designed to provide cells with both a physical barrier and an extracellular matrix to further improve the secretion of therapeutic proteins from cells This review will discuss (1) the cell encapsulation process, (2) the immunogenicity of the encapsulating hydrogel, (3) the transport properties of the hydrogel, (4) the hydrogel mechanical properties, and will propose new strategies to improve the hydrogel and cell interaction for successful cell-based drug delivery strategies

215 citations


Cites background from "Selection methods for high-producin..."

  • ...This provides the potential to treat various diseases that cannot be cured with currently available technologies.(6) A variety of stem cells, progenitor cells, lineage-committed cells, and genetically engineered cells are being tested in preclinical and clinical trials as drug delivery vehicles, as shown in Table I....

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References
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Journal ArticleDOI
11 Feb 1994-Science
TL;DR: A complementary DNA for the Aequorea victoria green fluorescent protein produces a fluorescent product when expressed in prokaryotic or eukaryotic cells, which can be used to monitor gene expression and protein localization in living organisms.
Abstract: A complementary DNA for the Aequorea victoria green fluorescent protein (GFP) produces a fluorescent product when expressed in prokaryotic (Escherichia coli) or eukaryotic (Caenorhabditis elegans) cells. Because exogenous substrates and cofactors are not required for this fluorescence, GFP expression can be used to monitor gene expression and protein localization in living organisms.

7,016 citations


"Selection methods for high-producin..." refers background in this paper

  • ...The green fluorescent protein (GFP) gene, from the jellyfish Aequeorea victoria has become an important reporter molecule of gene expression not just in mammalian cell culture, but also bacterial, fungal and insect systems and in transgenic animals and plants (Blumenthal et al., 1999; Chalfie et al., 1994; Plautz et al., 1996; Sarramegna et al., 2002; Suzuki et al., 2006)....

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Journal ArticleDOI
TL;DR: Recently, the productivity of mammalian cells cultivated in bioreactors has reached the gram per liter range in a number of cases, a more than 100-fold yield improvement over titers seen for similar processes in the mid-1980s.
Abstract: Cultivated mammalian cells have become the dominant system for the production of recombinant proteins for clinical applications because of their capacity for proper protein folding, assembly and post-translational modification. Thus, the quality and efficacy of a protein can be superior when expressed in mammalian cells versus other hosts such as bacteria, plants and yeast. Recently, the productivity of mammalian cells cultivated in bioreactors has reached the gram per liter range in a number of cases, a more than 100-fold yield improvement over titers seen for similar processes in the mid-1980s. This increase in volumetric productivity has resulted mainly from improvements in media composition and process control. Opportunities still exist for improving mammalian cell systems through further advancements in production systems as well as through vector and host cell engineering.

2,016 citations

Journal ArticleDOI
TL;DR: The results demonstrate that the production of more and better GFP variants is possible and worthwhile, and facilitates multicolor imaging of differential gene expression, protein localization or cell fate.

1,559 citations


"Selection methods for high-producin..." refers background in this paper

  • ...However, the development of modified forms of GFP to improve expression efficiencies, increase fluorescence intensity and thermostability, and reduce photobleaching ( Heim and Tsien, 1996; Siemering et al., 1996) may go some way to offset this issue....

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