Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome
Nathan E. Lewis,Xin Liu,Yuxiang Li,Harish Nagarajan,George Yerganian,Edward J. O’Brien,Aarash Bordbar,Anne M Roth,Jeffrey Rosenbloom,Chao Bian,Min Xie,Wenbin Chen,Ning Li,Deniz Baycin-Hizal,Haythem Latif,Jochen Förster,Michael J. Betenbaugh,Iman Famili,Xun Xu,Jun Wang,Bernhard O. Palsson +20 more
TLDR
This analysis identified hamster genes missing in different CHO cell lines, and detected >3.7 million single-nucleotide polymorphisms (SNPs), 551,240 indels and 7,063 copy number variations.Abstract:
Chinese hamster ovary (CHO) cells, first isolated in 1957, are the preferred production host for many therapeutic proteins. Although genetic heterogeneity among CHO cell lines has been well documented, a systematic, nucleotide-resolution characterization of their genotypic differences has been stymied by the lack of a unifying genomic resource for CHO cells. Here we report a 2.4-Gb draft genome sequence of a female Chinese hamster, Cricetulus griseus, harboring 24,044 genes. We also resequenced and analyzed the genomes of six CHO cell lines from the CHO-K1, DG44 and CHO-S lineages. This analysis identified hamster genes missing in different CHO cell lines, and detected >3.7 million single-nucleotide polymorphisms (SNPs), 551,240 indels and 7,063 copy number variations. Many mutations are located in genes with functions relevant to bioprocessing, such as apoptosis. The details of this genetic diversity highlight the value of the hamster genome as the reference upon which CHO cells can be studied and engineered for protein production.read more
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The Genome 10K Project: A Way Forward
TL;DR: The status of known vertebrate genome projects, recommend standards for pronouncing a genome as sequenced or completed, and the present and future vision of the landscape of Genome 10K are provided.
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The role of replicates for error mitigation in next-generation sequencing.
TL;DR: Sources of experimental errors in NGS and how replicates can be used to abate such errors are discussed.
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The art of CHO cell engineering: A comprehensive retrospect and future perspectives
TL;DR: This review provides a comprehensive summary of the most fundamental achievements in CHO cell engineering over the past three decades and discusses the potential of novel and innovative methodologies that might contribute to further enhancement of existing CHO based production platforms for biopharmaceutical manufacturing in the future.
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Engineered CHO cells for production of diverse, homogeneous glycoproteins.
Zhang Yang,Shengjun Wang,Adnan Halim,Morten Alder Schulz,Morten Frödin,Shamim Herbert Rahman,Malene Bech Vester-Christensen,Malene Bech Vester-Christensen,Carsten Behrens,Claus Kristensen,Sergey Y. Vakhrushev,Eric P. Bennett,Hans H. Wandall,Henrik Clausen +13 more
TL;DR: An engineering approach will aid the production of glycoproteins with improved properties and therapeutic potential by constructing a design matrix that facilitates the generation of desired glycosylation, such as human-like α2,6-linked sialic acid capping.
Journal ArticleDOI
A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism.
Hooman Hefzi,Kok Siong Ang,Michael Hanscho,Aarash Bordbar,David E. Ruckerbauer,Meiyappan Lakshmanan,Camila A. Orellana,Deniz Baycin-Hizal,Yingxiang Huang,Daniel Ley,Veronica Martinez,Sarantos Kyriakopoulos,Natalia E Jiménez,Daniel C. Zielinski,Lake-Ee Quek,Tune Wulff,Johnny Arnsdorf,Shangzhong Li,Jae Seong Lee,Giuseppe Paglia,Nicolás Loira,Philipp Spahn,Lasse Ebdrup Pedersen,Jahir M. Gutierrez,Zachary A. King,Anne Mathilde Lund,Harish Nagarajan,Alex Thomas,Alyaa M. Abdel-Haleem,Juergen Zanghellini,Helene Faustrup Kildegaard,Bjørn G. Voldborg,Ziomara P. Gerdtzen,Michael J. Betenbaugh,Bernhard O. Palsson,Mikael Rørdam Andersen,Lars K. Nielsen,Nicole Borth,Dong-Yup Lee,Dong-Yup Lee,Nathan E. Lewis +40 more
TL;DR: The models accurately predict growth phenotypes and known auxotrophies in CHO cells and show that the metabolic resources in CHO are more than three times more efficiently utilized for growth or recombinant protein synthesis following targeted efforts to engineer the CHO secretory pathway.
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