Pharmaceutical bioprocessing最新文献

{"title":"Industry perspective on Chinese hamster ovary cell 'omics'","authors":"Holger Laux","doi":"10.4155/PBP.14.48","DOIUrl":"https://doi.org/10.4155/PBP.14.48","url":null,"abstract":"The biopharmaceutical sector has become a significant segment of pharmaceutical industry. More than 200 biopharmaceutical products have reached market approval and more than 350 additional products are currently in clinical trials [1]. Chinese hamster ovary (CHO) cells are the main host for production of recombinant therapeutic proteins. The 2011 CHO-produced biopharmaceutical sales were nearly US$60 billion [2]. Approximately 45% of new products approved in the period from 2006 to 2010 produced in CHO cells and seven out of ten of the world’s top-selling biopharmaceutical drugs are expressed in CHO cells [1]. Despite some progress in improving therapeutic protein productivity, the cellular machinery of CHO cells is still not well understood and consequently good knowledge of recombinant protein production is missing. Therefore, functional genomics to better understand and improve productivity of CHO cell lines in pharmaceutical and biotech industry is getting more and more relevant. This includes applied genomic screening as well as cell line engineering tools. Thanks to recent advances in decoding the CHO cell genome and transcriptome [3–6] novel cell line engineering technologies as gene knockout (e.g., zinc finger nucleases [ZFNs], transcription activator-like effector nucleases [TALENs], clustered regularly interspaced short palindromic repeats [CRISPRs]), RNA interference (e.g., si/shRNA) as well as overexpression or introduction of new genes can now be applied to modify CHO cell lines. The expectation is that the now available Chinese hamster genomic information will lead to better understanding of the expression of recombinant proteins in CHO cells. This includes the utilization of genomics/ transcriptomic tools (e.g., next-generation sequencing [NGS], expression/comparative genomics microarray techniques), proteomic tools (e.g., mass spectrometry [MS]), as well as metabolomic techniques (e.g., nuclear magnetic resonance spectroscopy).","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"377-381"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.48","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to reconnect US academic and industrial researchers to better utilize Chinese hamster ovary ‘omics in bioprocessing","authors":"S. Harcum","doi":"10.4155/PBP.14.43","DOIUrl":"https://doi.org/10.4155/PBP.14.43","url":null,"abstract":"","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"383-388"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.43","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Chinese hamster ovary cell proteomics for biopharmaceutical processing","authors":"Amit Kumar, Kelley Heffner, J. Shiloach, M. Betenbaugh, Deniz Baycin-Hizal","doi":"10.4155/PBP.14.49","DOIUrl":"https://doi.org/10.4155/PBP.14.49","url":null,"abstract":"Chinese hamster ovary (CHO) cell lines are the preferred host for manufacturing therapeutic proteins. The use of proteomics for recombinant protein production in CHO cells has expanded recently because of the ease in identifying protein levels and its potential to elucidate targets for improved growth and productivity. Coupling advanced analytical methods, labeling strategies and bioinformatics with mass spectrometry-based proteomics facilitates identification and quantification of large numbers of proteins. CHO proteomics studies have increased the knowledge of proteins that affect cell culture events, thereby facilitating media development and cell line engineering to increase growth and production, delay apoptosis and utilize nutrients more effectively. The applications of proteomics offers numerous ways for creating superior hosts and improving biotherapeutics production in CHO cells.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"421-435"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.49","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward genome-scale models of the Chinese hamster ovary cells: incentives, status and perspectives","authors":"C. Kaas, Yuzhou Fan, D. Weilguny, C. Kristensen, H. F. Kildegaard, M. Andersen","doi":"10.4155/PBP.14.54","DOIUrl":"https://doi.org/10.4155/PBP.14.54","url":null,"abstract":"Bioprocessing of the important Chinese hamster ovary (CHO) cell lines used for the production of biopharmaceuticals stands at the brink of several redefining events. In 2011, the field entered the genomics era, which has accelerated omics-based phenotyping of the cell lines. In this review we describe one possible application of this data: the generation of computational models for predictive and descriptive analysis of CHO cellular metabolism. We describe relevant advances in other organisms and how they can be applied to CHO cells. The immediate implications of the implementation of these methods will be accelerated development of the next generation of CHO cell lines and derived biopharmaceuticals.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"437-448"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.54","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statistical methods for mining Chinese hamster ovary cell 'omics data: from differential expression to integrated multilevel analysis of the biological system","authors":"C. Clarke, N. Barron, P. Meleady, M. Clynes","doi":"10.4155/PBP.14.50","DOIUrl":"https://doi.org/10.4155/PBP.14.50","url":null,"abstract":"Publication of Chinese hamster ovary (CHO) cell line and Chinese hamster genomes is accelerating efforts to increase the efficiency of biopharmaceutical manufacturing through greater understanding of CHO cell biology. It is hoped that this knowledge will lead to more predictable bioprocesses through the identification of biomarkers for culture monitoring and engineering of the CHO cell itself. If we are to translate the potential of the CHO systems biology era to industrial practice, the extraction of knowledge from complex genomic, proteomic, transcriptomic and metabolomic datasets will be critical. In this manuscript, we review the methods utilized to analyze expression profiling data and highlight the role of advanced statistics as we generate larger scale datasets and move toward integrated multi-omic analyses of the biological system.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"469-481"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.50","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights on biomarkers from Chinese hamster ovary omics studies","authors":"Sarantos Kyriakopoulos, C. Kontoravdi","doi":"10.4155/PBP.14.45","DOIUrl":"https://doi.org/10.4155/PBP.14.45","url":null,"abstract":"As efforts for selecting high-producing cells during cell line development are moving toward the use of high-throughput, automated methods, there is considerable promise for identifying suitable markers arising from transcriptomic, proteomic and metabolomic studies. Herein we discuss the opportunities presented from recent characterization studies of high producers as well as comparisons with non- and lower-producing clones. We further put forward unique characteristics of cell lines with high productivity, which can be used for cell line screening and genetic engineering.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"389-401"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.45","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opening the black box: Chinese hamster ovary research goes genome scale","authors":"N. Borth","doi":"10.4155/PBP.14.42","DOIUrl":"https://doi.org/10.4155/PBP.14.42","url":null,"abstract":"The scientific community of Chinese hamster ovary (CHO)-cell scientists had a meeting to discuss the opportunities and requirements for a new era of genome scale science for CHO cells. With multiple genome sequences available, the challenge to the field is to use approaches of systems and synthetic biology to enhance quality and yield of recombinant therapeutics from CHO.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"367-369"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.42","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special Focus: an 'omics approach to Chinese hamster ovary based pharmaceutical bioprocessing","authors":"C. Clarke, Kelvin H. Lee","doi":"10.4155/PBP.14.51","DOIUrl":"https://doi.org/10.4155/PBP.14.51","url":null,"abstract":"Colin Clarke*,1 & Kelvin H Lee2 1The National Institute for Bioprocessing Research & Training, Dublin, Ireland 2Department of Chemical & Biomolecular Engineering, Delaware Biotechnology Institute, University of Delaware, Newark, DE 19711, USA *Author for correspondence: colin.clarke@nibrt.ie “...if recent advances in Chinese hamster ovary cell genome-scale science are to continue and the promise of better biopharmaceutical production is to become reality we must continue to foster collaboration between academics and researchers in industry.” Pharmaceutical Foreword","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"351-353"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.51","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chinese hamster ovary mutants for glycosylation engineering of biopharmaceuticals","authors":"P. Stanley","doi":"10.4155/PBP.14.37","DOIUrl":"https://doi.org/10.4155/PBP.14.37","url":null,"abstract":"The Chinese hamster ovary (CHO) cell has long been the cell of choice for the biopharmaceutical industry. The reasons for this are partly historical and partly because CHO cells produce glycoproteins with a glycan complement similar to that synthesized by human cells. The CHO-DUKX-B11 line was established early in the development of the biotechnology industry and has the advantage of allowing selection for high expression of transgenes. In addition, CHO cells glycosylate glycoproteins with a subset of glycans typical of human cells and essentially lacking antigenic sugar residues like α(1,3)Gal, β(1,2)xylose or N-glycolylneuraminic acid, typical of rodent or plant cells. In addition, CHO cells have a pseudo-haploid genome allowing stable mutants with desirable properties to be readily isolated. It is becoming increasingly evident that the manipulation of glycosylation pathways to produce secreted glycoprotein therapeutics with glycans appropriate for optimal half-life, cellular targeting and functional activity, is very important. This editorial will discuss CHO glycosylation mutants that are currently available, and the potential for glycosylation engineering to produce optimal biopharmaceuticals in the future. CHO cell mutants with altered glycosylation were initially isolated by selection for resistance to the cytotoxicity of plant lectins [1]. Cells selected for resistance to one lectin, were often resistant to others with related glycan binding properties, and also hypersensitive to lectins recognizing sugars that became newly terminal due to the nature of the glycosylation defect. By comparing resistance to a panel of plant lectins, lectin-resistant mutants could be grouped into lectin resistance phenotypes. In addition, somatic cell hybridization was used to define genetic complementation groups. Once genes encoding glycosylation activities were cloned, mutations giving rise to each complementation group were identified and numerous allelic series defined. There are now a large number of CHO glycosylation mutants with known genetic and biochemical defects that may be used to engineer glycoproteins in order to optimize their properties. These include mutants that generate glycoproteins with modified N-glycans and/or O-glycans [2], glycosaminoglycans [3] or glycophosphotidylinositol-linked glycans [4]. However, for these mutants to be useful in the industrial level production of glycoprotein therapeutics, a specific glycosylation mutant must be employed from the very beginning of engineering a cell line for high productivity. While it is often stated that existing CHO mutant lines are not high producers, this may Pamela Stanley Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10461, USA pamela.stanley@einstein.yu.edu “...manipulation of glycosylation to enhance the properties of glycoproteins can be performed at any stage of the development of a production cell line using CRISPR/Cas9 technology.” SPECIAL FOCUS y ","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"2 1","pages":"359-361"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.37","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70347968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycosylation analysis of Chinese hamster ovary produced glycoproteins","authors":"M. Spearman, Edward D Bodnar, H. Perreault, M. Butler","doi":"10.4155/PBP.14.53","DOIUrl":"https://doi.org/10.4155/PBP.14.53","url":null,"abstract":"Glycosylation is a critical quality attribute of biotherapeutics produced from mammalian cells. Small changes in the glycan structures may have profound effects on the efficacy and functions of the glycoprotein, such as fucosylation of the IgG glycan reducing the ability of the IgG to bind to the FcϒRIIIA receptor. Chinese hamster ovary produced glycoprotein biotherapeutics may contain antigenic glycan structures that must be defined and monitored. Therefore, structural analysis of glycans is a key component in the development and production of glycosylated products. We discuss the current techniques available for glycan, glycopeptide and whole glycoprotein analysis. We emphasize recent analytic developments in high-throughput automated methods, as well as, further refinement of methods for separation and identification of isomers and potentially antigenic structures.","PeriodicalId":90285,"journal":{"name":"Pharmaceutical bioprocessing","volume":"23 1","pages":"449-468"},"PeriodicalIF":0.0,"publicationDate":"2014-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4155/PBP.14.53","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70348528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}