Analysis and use of MAR elements to increase the production of recombinant proteins with mammalian cell lines in the pharmaceutical industry

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Projektnummer

6960.3;7 LSPP-LS

Projekttitel

Analysis and use of MAR elements to increase the production of recombinant proteins with mammalian cell lines in the pharmaceutical industry

Projekttitel Englisch

Analysis and use of MAR elements to increase the production of recombinant proteins with mammalian cell lines in the pharmaceutical industry

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Erfasste Texte

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Kurzbeschreibung (Englisch)	Analysis and use of MAR elements to increase the production of recombinant proteins with mammalian cell lines in the pharmaceutical industry
Abstract (Englisch)	At present, mammalian cell-based production of recombinant proteins for pharmaceutical purposes is suffering from a world-wide shortage, because of increasing needs and of the limited capacity of the facilities that can meet the quality expectations of governmental agencies such as the FDA. The rapid identification of stable high level producer cell lines is still one of the major challenges in biotechnology, as it is often hampered by the time-consuming characterization of numerous cell clones needed to isolate one with desired properties, and by the productivity of the cell lines that can be identified and analyzed in these time constraints. We previously screened different genetic elements for their ability to allow consistent high level expression of heterologous genes in eukaryotic cells, and the chicken lysozyme matrix-attachment region (MAR) was found to increase the proportion of high-producing CHO cell clones in cell population analysis, thus reducing the number of cell lines that need to be screened while increasing productivity (Zahn et al., J. Biotechnol. 2000; World pat. WO 02074969). In recent developments, we discovered that MARs can be dissected in smaller active elements, which biological and biophysical properties can be analyzed experimentally. Furthermore, new elements of this type may be identified from currently available genomic sequences, provided that bioinformatics tools can be developed, with the goal to construct even more potent genetic elements. The objective of the project proposed here will be the identification of novel MAR elements in genomes, their assembly in more active and shorter derivatives, and the demonstration of their performance is allowing enhanced proteins productions from mammalian cell lines.

Kategorie

Text

Kurzbeschreibung
(Englisch)

Analysis and use of MAR elements to increase the production of recombinant proteins with mammalian cell lines in the pharmaceutical industry

Abstract
(Englisch)

At present, mammalian cell-based production of recombinant proteins for pharmaceutical purposes is suffering from a world-wide shortage, because of increasing needs and of the limited capacity of the facilities that can meet the quality expectations of governmental agencies such as the FDA. The rapid identification of stable high level producer cell lines is still one of the major challenges in biotechnology, as it is often hampered by the time-consuming characterization of numerous cell clones needed to isolate one with desired properties, and by the productivity of the cell lines that can be identified and analyzed in these time constraints. We previously screened different genetic elements for their ability to allow consistent high level expression of heterologous genes in eukaryotic cells, and the chicken lysozyme matrix-attachment region (MAR) was found to increase the proportion of high-producing CHO cell clones in cell population analysis, thus reducing the number of cell lines that need to be screened while increasing productivity (Zahn et al., J. Biotechnol. 2000; World pat. WO 02074969). In recent developments, we discovered that MARs can be dissected in smaller active elements, which biological and biophysical properties can be analyzed experimentally. Furthermore, new elements of this type may be identified from currently available genomic sequences, provided that bioinformatics tools can be developed, with the goal to construct even more potent genetic elements. The objective of the project proposed here will be the identification of novel MAR elements in genomes, their assembly in more active and shorter derivatives, and the demonstration of their performance is allowing enhanced proteins productions from mammalian cell lines.