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Recent developments in miRNA based recombinant protein expression in CHO

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Abstract

It is widely accepted that the growing demand for recombinant therapeutic proteins has led to the expansion of the biopharmaceutical industry and the development of strategies to increase recombinant protein production in mammalian cell lines such as SP2/0 HEK and particularly Chinese hamster ovary cells. For a long time now, most investigations have been focused on increasing host cell productivity using genetic manipulating of cellular processes like cell cycle, apoptosis, cell growth, protein secretory and other pathways. In recent decades MicroRNAs beside different genetic engineering tools (e.g., TALEN, ZFN, and Crisper/Cas) have attracted further attention as a tool in the genetic engineering of host cells to increase protein expression levels. Their ability to simultaneously target multiple mRNAs involved in one or more cellular processes made them a favorable tool in this field. Accordingly, this study aimed to review the methods of selecting target miRNA for cell line engineering, miRNA gain- or loss-of-function strategies, examples of laboratory and pilot studies in this field and discussed advantages and disadvantages of this technology.

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References

  • Aguiar TQ, Santos SB, Martins IM, Domingues L, Oliveira C (2019) Production and bioengineering of recombinant pharmaceuticals. Proteins: sustainable source, processing and applications. Elsevier, Amsterdam, pp 259–293

    Chapter  Google Scholar 

  • Amadi IM, Agrawal V, Christianson T, Bardliving C, Shamlou P, LeBowitz JH (2020) Inhibition of endogenous miR-23a/miR-377 in CHO cells enhances difficult-to-express recombinant lysosomal sulfatase activity. Biotechnol Prog 36:e2974

    Article  CAS  PubMed  Google Scholar 

  • Amann T, Hansen AH, Kol S, Lee GM, Andersen MR, Kildegaard HF (2018) CRISPR/Cas9-multiplexed editing of Chinese hamster ovary B4Gal-T1, 2, 3, and 4 tailors N-glycan profiles of therapeutics and secreted host cell proteins. Biotechnol J 13:1800111

    Article  CAS  Google Scholar 

  • Amann T, Schmieder V, Faustrup Kildegaard H, Borth N, Andersen MR (2019) Genetic engineering approaches to improve posttranslational modification of biopharmaceuticals in different production platforms. Biotechnol Bioeng 116:2778–2796

    Article  CAS  PubMed  Google Scholar 

  • Barnes LM, Bentley CM, Dickson AJ (2004) Molecular definition of predictive indicators of stable protein expression in recombinant NS0 myeloma cells. Biotechnol Bioeng 85:115–121

    Article  CAS  PubMed  Google Scholar 

  • Bauer DE, Canver MC, Orkin SH (2015) Generation of genomic deletions in mammalian cell lines via CRISPR/Cas9. JoVE 83:e52118

    Google Scholar 

  • Brinkrolf K, Rupp O, Laux H, Kollin F, Ernst W, Linke B, Kofler R, Romand S, Hesse F, Budach WE (2013) Chinese hamster genome sequenced from sorted chromosomes. Nat Biotechnol 31:694–695

    Article  CAS  PubMed  Google Scholar 

  • Bryan L, Clynes M, Meleady P (2021) The emerging role of cellular post-translational modifications in modulating growth and productivity of recombinant Chinese hamster ovary cells. Biotechnol Adv 49:107757

    Article  CAS  PubMed  Google Scholar 

  • Chiang AWT, Li S, Kellman BP, Chattopadhyay G, Zhang Y, Kuo C-C, Gutierrez JM, Ghazi F, Schmeisser H, Ménard P, Bjørn SP, Voldborg BG, Rosenberg AS, Puig M, Lewis NE (2019) Combating viral contaminants in CHO cells by engineering innate immunity. Sci Rep 9:8827

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Clark MB, Johnston RL, Inostroza-Ponta M, Fox AH, Fortini E, Moscato P, Dinger ME, Mattick JS (2012) Genome-wide analysis of long noncoding RNA stability. Genome Res 22:885–898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dangi AK, Sinha R, Dwivedi S, Gupta SK, Shukla P (2018) Cell line techniques and gene editing tools for antibody production: a review. Front Pharmacol. https://doi.org/10.3389/fphar.2018.00630

    Article  PubMed  PubMed Central  Google Scholar 

  • Dumont J, Euwart D, Mei B, Estes S, Kshirsagar R (2016) Human cell lines for biopharmaceutical manufacturing: history, status, and future perspectives. Crit Rev Biotechnol 36:1110–1122

    Article  CAS  PubMed  Google Scholar 

  • Emmerling VV, Simon F, Fabian S, Karlheinz H, René H, Friedemann H, Markus H, Stefan K, Kerstin O (2016) Temperature-sensitive miR-483 is a conserved regulator of recombinant protein and viral vector production in mammalian cells. Biotechnol Bioeng 113:830–841

    Article  CAS  PubMed  Google Scholar 

  • Feichtinger J, Hernández I, Fischer C, Hanscho M, Auer N, Hackl M, Jadhav V, Baumann M, Krempl PM, Schmidl C (2016) Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time. Biotechnol Bioeng 113:2241–2253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fischer S, Buck T, Wagner A, Ehrhart C, Giancaterino J, Mang S, Schad M, Mathias S, Aschrafi A, Handrick R, Otte K (2014) A functional high-content miRNA screen identifies miR-30 family to boost recombinant protein production in CHO cells. Biotechnol J 9:1279–1292

    Article  CAS  PubMed  Google Scholar 

  • Fischer S, Handrick R, Aschrafi A, Otte K (2015a) Unveiling the principle of microRNA-mediated redundancy in cellular pathway regulation. RNA Biol 12:238–247

    Article  PubMed  PubMed Central  Google Scholar 

  • Fischer S, Handrick R, Otte K (2015b) The art of CHO cell engineering: a comprehensive retrospect and future perspectives. Biotechnol Adv 33:1878–1896

    Article  CAS  PubMed  Google Scholar 

  • Fischer S, Mathias S, Schaz S, Emmerling VV, Buck T, Kleemann M, Hackl M, Grillari J, Aschrafi A, Handrick R, Otte K (2015c) Enhanced protein production by microRNA-30 family in CHO cells is mediated by the modulation of the ubiquitin pathway. J Biotechnol 212:32–43

    Article  CAS  PubMed  Google Scholar 

  • Fischer S, Marquart KF, Pieper LA, Fieder J, Gamer M, Gorr I, Schulz P, Bradl H (2017) miRNA engineering of CHO cells facilitates production of difficult-to-express proteins and increases success in cell line development. Biotechnol Bioeng 114:1495–1510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gammell P, Barron N, Kumar N, Clynes M (2007) Initial identification of low temperature and culture stage induction of miRNA expression in suspension CHO-K1 cells. J Biotechnol 130:213–218

    Article  CAS  PubMed  Google Scholar 

  • Griffith A, Kelly PS, Vencken S, Lao NT, Greene CM, Clynes M, Barron N (2018) miR-CATCH identifies biologically active miRNA regulators of the pro-survival gene XIAP, in Chinese hamster ovary cells. Biotechnol J. https://doi.org/10.1002/biot.201700299

    Article  PubMed  Google Scholar 

  • Hackl M, Borth N, Grillari J (2012) The CHO miRNA transcriptome. In: Barron N (ed) MicroRNAs as tools in biopharmaceutical production. Springer, Dordrecht, pp 49–64

    Chapter  Google Scholar 

  • Hamdi A, Széliová D, Ruckerbauer DE, Rocha I, Borth N, Zanghellini J (2020) Key challenges in designing CHO chassis platforms. Processes 8:643

    Article  Google Scholar 

  • Hefzi H, Ang KS, Hanscho M, Bordbar A, Ruckerbauer D, Lakshmanan M, Orellana CA, Baycin-Hizal D, Huang Y, Ley D (2016) A consensus genome-scale reconstruction of Chinese hamster ovary cell metabolism. Cell Systems 3:434-443. e438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huhn S, Ou Y, Kumar A, Liu R, Du Z (2019) High throughput, efficacious gene editing & genome surveillance in Chinese hamster ovary cells. PLoS ONE 14:e0218653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inwood S, Betenbaugh MJ, Shiloach J (2018a) Methods for using small non-coding RNAs to improve recombinant protein expression in mammalian cells. Genes 9:25

    Article  PubMed Central  CAS  Google Scholar 

  • Inwood S, Buehler E, Betenbaugh M, Lal M, Shiloach J (2018b) Identifying HIPK1 as target of miR-22-3p enhancing recombinant protein production from HEK 293 cell by using microarray and HTP siRNA screen. Biotechnol J 13:1700342

    Article  CAS  Google Scholar 

  • Inwood S, Abaandou L, Betenbaugh M, Shiloach J (2020) Improved protein expression in HEK293 cells by over-expressing miR-22 and knocking-out its target gene, HIPK1. New Biotechnol 54:28–33

    Article  CAS  Google Scholar 

  • Jadhav V, Hackl M, Druz A, Shridhar S, Chung CY, Heffner KM, Kreil DP, Betenbaugh M, Shiloach J, Barron N, Grillari J, Borth N (2013) CHO microRNA engineering is growing up: recent successes and future challenges. Biotechnol Adv 31:1501–1513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jadhav V, Hackl M, Klanert G, Hernandez Bort JA, Kunert R, Grillari J, Borth N (2014) Stable overexpression of miR-17 enhances recombinant protein production of CHO cells. J Biotechnol 175:38–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jarroux J, Morillon A, Pinskaya M (2017) History, discovery, and classification of lncRNAs. In: Rao MRS (ed) Long non coding RNA biology. Springer, Singapore, pp 1–46

    Google Scholar 

  • Karbyshev MS, Grigoryeva ES, Volkomorov VV, Kremmer E, Huber A, Mitrofanova IV, Kaigorodova EV, Zavyalova MV, Kzhyshkowska JG, Cherdyntseva NV, Choynzonov EL (2018) Development of novel monoclonal antibodies for evaluation of transmembrane prostate androgen-induced protein 1 (TMEPAI) expression patterns in gastric cancer. Pathol Oncol Res 24:427–438

    Article  CAS  PubMed  Google Scholar 

  • Kellner K, Solanki A, Amann T, Lao N, Barron N (2018) Targeting miRNAs with CRISPR/Cas9 to improve recombinant protein production of CHO cells. Methods Mol Biol (Clifton, NJ) 1850:221–235

    Article  CAS  Google Scholar 

  • Kelly PS, Breen L, Gallagher C, Kelly S, Henry M, Lao NT, Meleady P, O’Gorman D, Clynes M, Barron N (2015a) Re-programming CHO cell metabolism using miR-23 tips the balance towards a highly productive phenotype. Biotechnol J 10:1029–1040

    Article  CAS  PubMed  Google Scholar 

  • Kelly PS, Gallagher C, Clynes M, Barron N (2015b) Conserved microRNA function as a basis for Chinese hamster ovary cell engineering. Biotech Lett 37:787–798

    Article  CAS  Google Scholar 

  • Kesik-Brodacka M (2018) Progress in biopharmaceutical development. Biotechnol Appl Biochem 65:306–322

    Article  CAS  PubMed  Google Scholar 

  • Kildegaard HF, Baycin-Hizal D, Lewis NE, Betenbaugh MJ (2013) The emerging CHO systems biology era: harnessing the ‘omics revolution for biotechnology. Curr Opin Biotechnol 24:1102–1107

    Article  PubMed  CAS  Google Scholar 

  • Kim JY, Kim YG, Lee GM (2012) CHO cells in biotechnology for production of recombinant proteins: current state and further potential. Appl Microbiol Biotechnol 93:917–930

    Article  CAS  PubMed  Google Scholar 

  • Klanert G, Jadhav V, Shanmukam V, Diendorfer A, Karbiener M, Scheideler M, Bort JH, Grillari J, Hackl M, Borth N (2016) A signature of 12 microRNAs is robustly associated with growth rate in a variety of CHO cell lines. J Biotechnol 235:150–161

    Article  CAS  PubMed  Google Scholar 

  • Klanert G, Fernandez DJ, Weinguny M, Eisenhut P, Bühler E, Melcher M, Titus SA, Diendorfer AB, Gludovacz E, Jadhav V (2019) A cross-species whole genome siRNA screen in suspension-cultured Chinese hamster ovary cells identifies novel engineering targets. Sci Rep 9:1–11

    Article  CAS  Google Scholar 

  • Koh TC, Lee YY, Chang SQ, Nissom PM (2009) Identification and expression analysis of miRNAs during batch culture of HEK-293 cells. J Biotechnol 140:149–155

    Article  CAS  PubMed  Google Scholar 

  • Kremkow BG, Baik JY, MacDonald ML, Lee KH (2015) CHOgenome.org 2.0: genome resources and website updates. Biotechnol J 10:931–938

    Article  CAS  PubMed  Google Scholar 

  • Leroux AC, Bartels E, Winter L, Mann M, Otte K, Zehe C (2020) Transferability of miRNA-technology to bioprocessing: influence of cultivation mode and media. Biotechnol Prog. https://doi.org/10.1002/btpr.3107

    Article  PubMed  PubMed Central  Google Scholar 

  • Lim Y, Wong NS, Lee YY, Ku SC, Wong DC, Yap MG (2010) Engineering mammalian cells in bioprocessing—current achievements and future perspectives. Biotechnol Appl Biochem 55:175–189

    Article  CAS  PubMed  Google Scholar 

  • Liszewski K (2019) Taking cell lines to the bank: in biopharmaceutical development, master cell banks reward those who invest in cell line optimization. Genet Eng Biotechnol News 39:42–45

    Article  Google Scholar 

  • Loh WP, Yang Y, Lam KP (2017) miR-92a enhances recombinant protein productivity in CHO cells by increasing intracellular cholesterol levels. Biotechnol J. https://doi.org/10.1002/biot.201600488

    Article  PubMed  Google Scholar 

  • Martinez-Lopez JE, Coleman O, Meleady P, Clynes M (2021) Transfection of miR-31* boosts oxidative phosphorylation metabolism in the mitochondria and enhances recombinant protein production in Chinese hamster ovary cells. J Biotechnol. https://doi.org/10.1016/j.jbiotec.2021.04.012

    Article  PubMed  Google Scholar 

  • McVey D, Aronov M, Rizzi G, Cowan A, Scott C, Megill J, Russell R, Tirosh B (2016) CHO cells knocked out for TSC2 display an improved productivity of antibodies under fed batch conditions. Biotechnol Bioeng 113:1942–1952

    Article  CAS  PubMed  Google Scholar 

  • Meyer HJ, Reilly D, Martin SE, Wong AW (2017) Identification of a novel miRNA that increases transient protein expression in combination with valproic acid. Biotechnol Prog 33:1139–1145

    Article  CAS  PubMed  Google Scholar 

  • Muluhngwi P, Richardson K, Napier J, Rouchka EC, Mott JL, Klinge CM (2017) Regulation of miR-29b-1/a transcription and identification of target mRNAs in CHO-K1 cells. Mol Cell Endocrinol 444:38–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Flaherty R, Bergin A, Flampouri E, Mota LM, Obaidi I, Quigley A, Xie Y, Butler M (2020) Mammalian cell culture for production of recombinant proteins: a review of the critical steps in their biomanufacturing. Biotechnol Adv 43:107552

    Article  PubMed  CAS  Google Scholar 

  • Omasa T, Onitsuka M, Kim W-D (2010) Cell engineering and cultivation of Chinese hamster ovary (CHO) cells. Curr Pharm Biotechnol 11:233–240

    Article  CAS  PubMed  Google Scholar 

  • Park JS, Kim H, Park J, Yu S, Kim D, Lee J, Oh H, Baek K, Yoon J (2010a) Overproduction of recombinant human hepatocyte growth factor in Chinese hamster ovary cells. Protein Expr Purif 70:231–235

    Article  CAS  PubMed  Google Scholar 

  • Park JY, Takagi Y, Yamatani M, Honda K, Asakawa S, Shimizu N, Omasa T, Ohtake H (2010b) Identification and analysis of specific chromosomal region adjacent to exogenous Dhfr-amplified region in Chinese hamster ovary cell genome. J Biosci Bioeng 109:504–511

    Article  CAS  PubMed  Google Scholar 

  • Peng Y, Croce C (2016) The role of MicroRNAs in human cancer. Sig Transduct Target Ther 1:15004

    Article  Google Scholar 

  • Pfizenmaier J, Junghans L, Teleki A, Takors R (2016) Hyperosmotic stimulus study discloses benefits in ATP supply and reveals miRNA/mRNA targets to improve recombinant protein production of CHO cells. Biotechnol J 11:1037–1047

    Article  CAS  PubMed  Google Scholar 

  • Quinn JJ, Chang HY (2016) Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet 17:47

    Article  CAS  PubMed  Google Scholar 

  • Raab N, Mathias S, Alt K, Handrick R, Fischer S, Schmieder V, Jadhav V, Borth N, Otte K (2019) CRISPR/Cas9-mediated knockout of MicroRNA-744 improves antibody titer of CHO production cell lines. Biotechnol J 14:1800477

    Article  CAS  Google Scholar 

  • Ratti M, Lampis A, Ghidini M, Salati M, Mirchev MB, Valeri N, Hahne JC (2020) MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) as new tools for cancer therapy: first steps from bench to bedside. Target Oncol 15:261–278

    Article  PubMed  PubMed Central  Google Scholar 

  • Rosenbloom KR, Armstrong J, Barber GP, Casper J, Clawson H, Diekhans M, Dreszer TR, Fujita PA, Guruvadoo L, Haeussler M, Harte RA, Heitner S, Hickey G, Hinrichs AS, Hubley R, Karolchik D, Learned K, Lee BT, Li CH, Miga KH, Nguyen N, Paten B, Raney BJ, Smit AFA, Speir ML, Zweig AS, Haussler D, Kuhn RM, Kent WJ (2015) The UCSC Genome Browser database: 2015 update. Nucleic Acids Res 43:D670-681

    Article  CAS  PubMed  Google Scholar 

  • Rupp O, MacDonald ML, Li S, Dhiman H, Polson S, Griep S, Heffner K, Hernandez I, Brinkrolf K, Jadhav V (2018) A reference genome of the Chinese hamster based on a hybrid assembly strategy. Biotechnol Bioeng 115:2087–2100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanchez N, Gallagher M, Lao N, Gallagher C, Clarke C, Doolan P, Aherne S, Blanco A, Meleady P, Clynes M, Barron N (2013) MiR-7 triggers cell cycle arrest at the G1/S transition by targeting multiple genes including Skp2 and Psme3. PLoS ONE 8:e65671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sander J, Joung J (2014) CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol 32:347–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schoellhorn M, Fischer S, Wagner A, Handrick R, Otte K (2017) miR-143 targets MAPK7 in CHO cells and induces a hyperproductive phenotype to enhance production of difficult-to-express proteins. Biotechnol Prog 33:1046–1058

    Article  CAS  PubMed  Google Scholar 

  • Sergeeva D, Camacho-Zaragoza JM, Lee JS, Kildegaard HF (2019) CRISPR/Cas9 as a genome editing tool for targeted gene integration in CHO cells, CRISPR gene editing. Springer, New York, pp 213–232

    Google Scholar 

  • Simon F, Jesuran PA, Andreas W, Sven M, Melanie G, Franziska S, Martin D, Jörg Z, René H, Friedemann H, Kerstin O (2015) miR-2861 as novel HDAC5 inhibitor in CHO cells enhances productivity while maintaining product quality. Biotechnol Bioeng 112:2142–2153

    Article  CAS  Google Scholar 

  • Strotbek M, Florin L, Koenitzer J, Tolstrup A, Kaufmann H, Hausser A, Olayioye MA (2013) Stable microRNA expression enhances therapeutic antibody productivity of Chinese hamster ovary cells. Metab Eng 20:157–166

    Article  CAS  PubMed  Google Scholar 

  • Swiech K, Picanço-Castro V, Covas DT (2012) Human cells: new platform for recombinant therapeutic protein production. Protein Expr Purif 84:147–153

    Article  CAS  PubMed  Google Scholar 

  • Tang P, Xu J, Louey A, Tan Z, Yongky A, Liang S, Li ZJ, Weng Y, Liu S (2020) Kinetic modeling of Chinese hamster ovary cell culture: factors and principles. Crit Rev Biotechnol 40:265–281

    Article  CAS  PubMed  Google Scholar 

  • Tihanyi B, Nyitray L (2021) Recent advances in CHO cell line development for recombinant protein production. Drug Discov Today Technol. https://doi.org/10.1016/j.ddtec.2021.02.003

    Article  Google Scholar 

  • Valastyan S, Weinberg RA (2009) Assaying microRNA loss-of-function phenotypes in mammalian cells: emerging tools and their potential therapeutic utility. RNA Biol 6:541–545

    Article  CAS  PubMed  Google Scholar 

  • Valdés-Bango Curell R (2020) MicroRNAs as metabolic sensors and engineering tools in CHO cells. PhD Thesis, National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University

  • Vito D, Smales CM (2018) The long non-coding RNA transcriptome landscape in CHO cells under batch and fed-batch conditions. Biotechnol J 13:1800122

    Article  CAS  Google Scholar 

  • Wang Z (2011) The guideline of the design and validation of MiRNA mimics, MicroRNA and cancer. Springer, New York, pp 211–223

    Google Scholar 

  • Weis BL, Guth N, Fischer S, Wissing S, Fradin S, Holzmann KH, Handrick R, Otte K (2018) Stable miRNA overexpression in human CAP cells: engineering alternative production systems for advanced manufacturing of biologics using miR-136 and miR-3074. Biotechnol Bioeng. https://doi.org/10.1002/bit.26715

    Article  PubMed  Google Scholar 

  • Wurm FM (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22:1393–1398

    Article  CAS  PubMed  Google Scholar 

  • Xiao S, Chen YC, Betenbaugh MJ, Martin SE, Shiloach J (2015) MiRNA mimic screen for improved expression of functional neurotensin receptor from HEK 293 cells. Biotechnol Bioeng 112:1632–1643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu X, Nagarajan H, Lewis NE, Pan S, Cai Z, Liu X, Chen W, Xie M, Wang W, Hammond S (2011) The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line. Nat Biotechnol 29:735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu C, Han Q, Zhou Q, Zhang L, Wu P, Lu Y, Si Y, Ma T, Ma B, Zhang B (2019) MiR-106b promotes therapeutic antibody expression in CHO cells by targeting deubiquitinase CYLD. Appl Microbiol Biotechnol 103:7085–7095

    Article  CAS  PubMed  Google Scholar 

  • Yang B, McJunkin K (2020) CRISPR screening strategies for microRNA target identification. FEBS J 287:2914–2922

    Article  CAS  PubMed  Google Scholar 

  • Yoshikawa T, Nakanishi F, Ogura Y, Oi D, Omasa T, Katakura Y, Kishimoto M, Suga K (2000) Amplified gene location in chromosomal DNA affected recombinant protein production and stability of amplified genes. Biotechnol Prog 16:710–715

    Article  CAS  PubMed  Google Scholar 

  • Yusufi FNK, Lakshmanan M, Ho YS, Loo BLW, Ariyaratne P, Yang Y, Ng SK, Tan TRM, Yeo HC, Lim HL (2017) Mammalian systems biotechnology reveals global cellular adaptations in a recombinant CHO cell line. Cell Syst 4:530-542. e536

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We also thank Dr. Morteza Karimipour and Dr.Marjan Mohammadi (PhD) for their general support and editorial assistance.

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The authors acknowledge the financial support received from the National Science Foundation (INSF) Development Program (INSF ID No.92006929), for their support and encouragement in carrying out this work.

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Bazaz, M., Adeli, A., Azizi, M. et al. Recent developments in miRNA based recombinant protein expression in CHO. Biotechnol Lett 44, 671–681 (2022). https://doi.org/10.1007/s10529-022-03250-1

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