Comparison of Internal Ribosome Entry Site (IRES) and Furin-2A (F2A) for Monoclonal Antibody Expression Level and Quality in CHO Cells

PLoS ONE

Volumn 8, Issue 5, 2013, Pages

  Ho, Steven C L ^a   Bardor, Muriel ^a,b   Li, Bin ^a   Lee, Jia Juan ^a   Song, Zhiwei ^a   Tong, Yen Wah ^c   Goh, Lin Tang ^a   Yang, Yuansheng ^a,d  

^a AGENCY FOR SCIENCE   (Singapore)

^b UNIVERSITÉ DE ROUEN   (France)

^c NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^d Nanyang Technological University   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

DIHYDROFOLATE REDUCTASE; FURIN; FURIN 2A; IMMUNOGLOBULIN; IMMUNOGLOBULIN G1 HEAVY CHAIN; IMMUNOGLOBULIN G1 LIGHT CHAIN; MONOCLONAL ANTIBODY; SIGNAL PEPTIDE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL AGGREGATION; CELL GROWTH; CHO CELL; CISTRON; CONTROLLED STUDY; EXPRESSION VECTOR; GENE EXPRESSION; GENETIC TRANSFECTION; INTERNAL RIBOSOME ENTRY SITE; MOLECULAR SIZE; NONHUMAN; PROTEIN CLEAVAGE;

AMINO ACID SEQUENCE; ANIMALS; ANTIBODIES, MONOCLONAL; BLOTTING, WESTERN; CHO CELLS; CHROMATOGRAPHY, GEL; CHROMATOGRAPHY, LIQUID; CRICETINAE; CRICETULUS; ELECTROPHORESIS, POLYACRYLAMIDE GEL; FURIN; GENETIC VECTORS; IMMUNOGLOBULIN G; IMMUNOGLOBULIN HEAVY CHAINS; IMMUNOGLOBULIN LIGHT CHAINS; MASS SPECTROMETRY; MOLECULAR SEQUENCE DATA; PEPTIDE MAPPING; RECEPTOR, ERBB-2; RIBOSOMES; TRANSFECTION; TUMOR NECROSIS FACTOR-ALPHA; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84877962654     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0063247     Document Type: Article

References (56)

1. Aggarwal S, (2010) What's fueling the biotech engine-2009-2010. Nature Biotechnology 28: 1165-1171.
2. Nelson AL, Dhimolea E, Reichert JM, (2010) Development trends for human monoclonal antibody therapeutics. Nature Reviews Drug Discovery 9: 767-774.
3. Birch JR, Racher AJ, (2006) Antibody production. Advanced Drug Delivery Reviews 58: 671-685.
4. Kim SJ, Kim NS, Ryu CJ, Hong HJ, Lee GM, (1998) Characterization of chimeric antibody producing CHO cells in the course of dihydrofolate reductase-mediated gene amplification and their stability in the absence of selective pressure. Biotechnology and Bioengineering 58: 73-84.
5. Rita Costa A, Elisa Rodrigues M, Henriques M, Azeredo J, Oliveira R, (2010) Guidelines to cell engineering for monoclonal antibody production. European Journal of Pharmaceutics and Biopharmaceutics 74: 127-138.
6. Wurm FM, (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nature Biotechnology 22: 1393-1398.
7. Barnes LM, Bentley CM, Moy N, Dickson AJ, (2007) Molecular analysis of successful cell line selection in transfected GS-NS0 myeloma cells. Biotechnology and Bioengineering 96: 337-348.
8. Ng SK, Lin W, Sachdeva R, Wang DI, Yap MG, (2010) Vector fragmentation: characterizing vector integrity in transfected clones by Southern blotting. Biotechnology Progress 26: 11-20.
9. Lee YK, Brewer JW, Hellman R, Hendershot LM, (1999) BiP and immunoglobulin light chain cooperate to control the folding of heavy chain and ensure the fidelity of immunoglobulin assembly. Molecular Biology of the Cell 10: 2209-2219.
10. Chusainow J, Yang YS, Yeo JH, Toh PC, Asvadi P, et al. (2009) A study of monoclonal antibody-producing CHO cell lines: what makes a stable high producer? Biotechnology and Bioengineering 102: 1182-1196.
11. Gonzalez R, Andrews BA, Asenjo JA, (2002) Kinetic model of BiP- and PDI-mediated protein folding and assembly. Journal of Theoretical Biology 214: 529-537.
12. Ho SCL, Bardor M, Feng H, Mariati, Tong YW, et al. (2012) IRES-mediated Tricistronic vectors for enhancing generation of high monoclonal antibody expressing CHO cell lines. Journal of Biotechnology 157: 130-139.
13. Li J, Zhang C, Jostock T, Dübel S, (2007) Analysis of IgG heavy chain to light chain ratio with mutant Encephalomyocarditis virus internal ribosome entry site. Protein Engineering, Design and Selection 20: 491-496.
14. Jiang Z, Huang Y, Sharfstein ST, (2006) Regulation of recombinant monoclonal antibody production in chinese hamster ovary cells: a comparative study of gene copy number, mRNA level, and protein expression. Biotechnology Progress 22: 313-318.
15. Schlatter S, Stansfield SH, Dinnis DM, Racher AJ, Birch JR, et al. (2005) On the optimal ratio of heavy to light chain genes for efficient recombinant antibody production by CHO cells. Biotechnology Progress 21: 122-133.
16. Lee CJ, Seth G, Tsukuda J, Hamilton RW, (2009) A clone screening method using mRNA levels to determine specific productivity and product quality for monoclonal antibodies. Biotechnology and Bioengineering 102: 1107-1118.
17. Lenny N, Green M, (1991) Regulation of endoplasmic reticulum stress proteins in COS cells transfected with immunoglobulin μ heavy chain cDNA. Journal Of Biological Chemistry 266: 20532-20537.
18. Fagioli C, Mezghrani A, Sitia R, (2001) Reduction of Interchain Disulfide Bonds Precedes the Dislocation of Ig-μ Chains from the Endoplasmic Reticulum to the Cytosol for Proteasomal Degradation. Journal Of Biological Chemistry 276: 40962-40967.
19. Hellen CUT, Sarnow P, (2001) Internal ribosome entry sites in eukaryotic mRNA molecules. Genes & Development 15: 1593-1612.
20. Mountford PS, Smith AG, (1995) Internal Ribosome Entry Sites And Dicistronic Rnas In Mammalian Transgenesis. Trends In Genetics 11: 179-184.
21. Houdebine LM, Attal J, (1999) Internal ribosome entry sites (IRESs): reality and use. Transgenic Research 8: 157-177.
22. Kaufman RJ, Davies MV, Wasley LC, Michnick D, (1991) Improved Vectors For Stable Expression Of Foreign Genes In Mammalian-Cells By Use Of The Untranslated Leader Sequence From Emc Virus. Nucleic Acids Research 19: 4485-4490.
23. Hennecke M, Kwissa M, Metzger K, Oumard A, Kroger A, et al. (2001) Composition and arrangement of genes define the strength of IRES-driven translation in bicistronic mRNAs. Nucleic Acids Research 29: 3327-3334.
24. Jostock T, Vanhove M, Brepoels E, van Gool R, Daukandt M, et al. (2004) Rapid generation of functional human IgG antibodies derived from Fab-on-phage display libraries. Journal of Immunological Methods 289: 65-80.
25. Li J, Menzel C, Meier D, Zhang C, Dubel S, et al. (2007) A comparative study of different vector designs for the mammalian expression of recombinant IgG antibodies. Journal of Immunological Methods 318: 113-124.
26. Li JD, Zhang CC, Jostock T, Dubel S, (2007) Analysis of IgG heavy chain to light chain ratio with mutant Encephalomyocarditis virus internal ribosome entry site. Protein Engineering Design & Selection 20: 491-496.
27. Mielke C, Tümmler M, Schübeler D, Von Hoegen I, Hauser H, (2000) Stabilized, long-term expression of heterodimeric proteins from tricistronic mRNA. Gene 254: 1-8.
28. Doronina VA, de Felipe P, Wu C, Sharma P, Sachs MS, et al. (2008) Dissection of a co-translational nascent chain separation event. Biochemical Society Transactions 36: 712-716.
29. Doronina VA, Wu C, de Felipe P, Sachs MS, Ryan MD, et al. (2008) Site-specific release of nascent chains from ribosomes at a sense codon. Molecular and Cellular Biology 28: 4227-4239.
30. de Felipe P, Luke GA, Hughes LE, Gani D, Halpin C, et al. (2006) E unum pluribus: multiple proteins from a self-processing polyprotein. Trends in Biotechnology 24: 68-75.
31. Donnelly ML, Luke G, Mehrotra A, Li X, Hughes LE, et al. (2001) Analysis of the aphthovirus 2A/2B polyprotein 'cleavage' mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal 'skip'. Journal of General Virology 82: 1013-1025.
32. Fang J, Qian JJ, Yi S, Harding TC, Tu GH, et al. (2005) Stable antibody expression at therapeutic levels using the 2A peptide. Nature Biotechnology 23: 584-590.
33. Fang J, Yi S, Simmons A, Tu GH, Nguyen M, et al. (2007) An antibody delivery system for regulated expression of therapeutic levels of monoclonal antibodies In Vivo. Molecular Therapy 15: 1153-1159.
34. Davies SL, O'Callaghan PM, McLeod J, Pybus LP, Sung YH, et al. (2011) Impact of gene vector design on the control of recombinant monoclonal antibody production by chinese hamster ovary cells. Biotechnology Progress 27: 1689-1699.
35. Camper N, Byrne T, Burden RE, Lowry J, Gray B, et al. (2011) Stable expression and purification of a functional processed Fab' fragment from a single nascent polypeptide in CHO cells expressing the mCAT-1 retroviral receptor. Journal of Immunological Methods 372: 30-41.
36. Jostock T, Dragic Z, Fang J, Jooss K, Wilms B, et al. (2010) Combination of the 2A/furin technology with an animal component free cell line development platform process. Applied Microbiology and Biotechnology 87: 1517-1524.
37. Li M, Wu YM, Qiu YH, Yao ZY, Liu SL, et al. (2012) 2A Peptide-based, Lentivirus-mediated Anti-death Receptor 5 Chimeric Antibody Expression Prevents Tumor Growth in Nude Mice. Molecular Therapy 20: 46-53.
38. Ng SK, Wang DIC, Yap MGS, (2007) Application of destabilizing sequences on selection marker for improved recombinant protein productivity in CHO-DG44. Metabolic Engineering 9: 304-316.
39. Rees S, Coote J, Stables J, Goodson S, Harris S, et al. (1996) Bicistronic vector for the creation of stable mammalian cell lines that predisposes all antibiotic-resistant cells to express recombinant protein. Biotechniques 20: 102-104, 106, 108-110.
40. Gonzalez R, Andrews BA, Asenjo JA, (2002) Kinetic model of BiP- and PDI-mediated protein folding and assembly. J Theor Biol 214: 529-537.
41. Kaminski A, Howell MT, Jackson RJ, (1990) Initiation of encephalomyocarditis virus RNA translation: The authentic initiation site is not selected by a scanning mechanism. Embo Journal 9: 3753-3759.
42. Bochkov YA, Palmenberg AC (2006) Translational efficiency of EMCV IRES in bicistronic vectors is dependent upon IRES sequence and gene location. Biotechniques 41: 283-284, 286, 288 passim.
43. Davies MV, Kaufman RJ, (1992) The Sequence Context Of The Initiation Codon In The Encephalomyocarditis Virus Leader Modulates Efficiency Of Internal Translation Initiation. Journal Of Virology 66: 1924-1932.
44. Kaminski A, Belsham GJ, Jackson RJ, (1994) Translation Of Encephalomyocarditis Virus-Rna- Parameters Influencing The Selection Of The Internal Initiation Site. Embo Journal 13: 1673-1681.
45. Martin P, Albagli O, Poggi MC, Boulukos KE, Pognonec P, (2006) Development of a new bicistronic retroviral vector with strong IRES activity. BMC Biotechnology 6: 4.
46. Qiao J, Roy V, Girard MH, Caruso M, (2002) High translation efficiency is mediated by the encephalomyocarditis virus internal ribosomal entry sites if the natural sequence surrounding the eleventh AUG is retained. Human Gene Therapy 13: 881-887.
47. Walter P, Blobel G, (1983) Subcellular distribution of signal recognition particle and 7SL-RNA determined with polypeptide-specific antibodies and complementary DNA probe. The Journal of cell biology 97: 1693-1699.
48. von Heijne G, (1985) Signal sequences: The limits of variation. Journal of Molecular Biology 184: 99-105.
49. Nothwehr SF, Gordon JI, (1990) Structural features in the NH2-terminal region of a model eukaryotic signal peptide influence the site of its cleavage by signal peptidase. Journal of Biological Chemistry 265: 17202-17208.
50. Kyte J, Doolittle RF, (1982) A simple method for displaying the hydropathic character of a protein. Journal of Molecular Biology 157: 105-132.
51. De Felipe P, Luke GA, Brown JD, Ryan MD, (2010) Inhibition of 2A-mediated 'cleavage' of certain artificial polyproteins bearing N-terminal signal sequences. Biotechnology Journal 5: 213-223.
52. Petersen TN, Brunak S, von Heijne G, Nielsen H, (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions. Nature Methods 8: 785-786.
53. Chan HY, Sivakamasundari V, Xing X, Kraus P, Yap SP, et al. (2011) Comparison of IRES and F2A-based locus-specific multicistronic expression in stable mouse lines. PLoS One 6.
54. Feige MJ, Hendershot LM, Buchner J, (2010) How antibodies fold. Trends in Biochemical Sciences 35: 189-198.
55. Nakayama K, (1997) Furin: A mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins. Biochemical Journal 327: 625-635.
56. Szymczak-Workman AL, Vignali KM, Vignali DAA, (2012) Design and Construction of 2A Peptide-Linked Multicistronic Vectors. Cold Spring Harbor Protocols 2012: 199-204.