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• W2922112009 abstract "Recombinant mammalian cell line development is a critical step in the current manufacturing process for large-scale production of therapeutic proteins. The current process of cell line development using random transgene integration induces high phenotypic heterogeneity among recombinant clones, thus limiting predictive value, process streamlining, and cost-effectiveness in biopharmaceutical drug discovery and development. Recent advances in genome-editing technologies and systems biology approaches offer new insight into cell line development to minimize clonal variation. Targeted engineering strategies, combined with engineering target/integration site discovery based on multiomics data sets and in silico models, have the potential to streamline the process of cell line development with highly predictable gene expression among recombinant clones. Mammalian expression platforms are primary production systems for therapeutic proteins that require complex post-translational modifications. Current processes used for developing recombinant mammalian cell lines generate clonal cell lines with high phenotypic heterogeneity, which has puzzled researchers that use mammalian cell culture systems for a long time. Advances in mammalian genome-editing technologies and systems biotechnology have shed light on clonal variation and enabled rational cell engineering in a targeted manner. We propose a new approach for a next-generation cell line development platform that can minimize clonal variation. Combined with the knowledge-based selection of ideal integration sites and engineering targets, targeted integration-based cell line development will allow tailored control of recombinant gene expression with predicted phenotypes. Mammalian expression platforms are primary production systems for therapeutic proteins that require complex post-translational modifications. Current processes used for developing recombinant mammalian cell lines generate clonal cell lines with high phenotypic heterogeneity, which has puzzled researchers that use mammalian cell culture systems for a long time. Advances in mammalian genome-editing technologies and systems biotechnology have shed light on clonal variation and enabled rational cell engineering in a targeted manner. We propose a new approach for a next-generation cell line development platform that can minimize clonal variation. Combined with the knowledge-based selection of ideal integration sites and engineering targets, targeted integration-based cell line development will allow tailored control of recombinant gene expression with predicted phenotypes. molecular biology technique used to analyze physical chromatin interactions within the nucleus. This technique involves crosslinking of chromatin segments that are in close spatial proximity, followed by fragmentation, ligation, and sequencing. Depending on ligation product detection methods, various 3C-based methods (e.g., 4C and Hi-C) possessing different scope of interaction profiles are available. alterable nature of genomes indicated by structural variation and aneuploidy; these characteristics are typically observed in immortalized mammalian cell lines. computational model encompassing all metabolic reactions that allow for the computation of whole-cell metabolism and prediction of cell growth and gene essentiality. genetic recombination process essential for DNA damage repair. A break in chromosomal DNA can be repaired by the exchange of nucleotide sequences between two similar DNA strands. cellular system for the expression of target molecules (genes). Mammalian cells are the main hosts for the production of various therapeutic proteins. computational model that allows for the analysis of cell phenotypes or biological processes. cryopreserved aliquot of (recombinant clonal) cells that are passaged as little as possible to prevent genetic variation, contamination, or loss of transgene expression. datasets of multiomes including genome, transcriptome, epigenome, proteome, metabolome, and lipidome. clonal cell line derived from host cells in which a transgene expression construct is introduced and stably integrated into the genome. powerful tool for targeted integration of transgenes in which site-specific recombinases exchange one (reporter) gene cassette flanked by a pair of incompatible heterospecific recombinase recognition sites for another (target transgene) cassette flanked by an identical pair of sites. parameter describing cell growth for a specific cell line in culture, defined as the rate of cell growth per unit time. parameter describing the capability of a specific cell line to generate its product in culture, defined as amount of product produced per cell per unit time (picogram per cell per day, PCD). inherently noisy and probabilistic gene expression profiles arising from fluctuations in transcription and translation. structural and quantitative chromosomal rearrangements including deletions, duplications, inversion, insertions, and translocations. clonal cell line derived from parental recombinant clonal cells by additional cloning procedures. megabase-sized genomic regions where chromatin contacts are favored and separated by boundary regions that are enriched in architectural proteins such as insulator binding factor and transposable elements or housekeeping genes." @default.
• W2922112009 created "2019-03-22" @default.
• W2922112009 creator A5030163258 @default.
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• W2922112009 date "2019-09-01" @default.
• W2922112009 modified "2023-10-11" @default.
• W2922112009 title "Mitigating Clonal Variation in Recombinant Mammalian Cell Lines" @default.
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• W2922112009 doi "https://doi.org/10.1016/j.tibtech.2019.02.007" @default.
• W2922112009 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30898338" @default.
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