Identifying low-level sequence variants via next generation sequencing to aid stable CHO cell line screening

Biotechnology Progress

Volumn 31, Issue 4, 2015, Pages 1077-1085

  Zhang, Sheng ^a   Bartkowiak, Lisa ^a   Nabiswa, Bernard ^a   Mishra, Pratibha ^a   Fann, John ^a   Ouellette, David ^a   Correia, Ivan ^a   Regier, Dean ^a   Liu, Junjian ^a  

^a ABBVIE INC   (United States)

Author keywords

CHO cell line; Next generation sequencing; Point mutation; Recombinant monoclonal antibody; Sequence variants

Indexed keywords

AMINO ACIDS; CELL CULTURE; MONOCLONAL ANTIBODIES; RECOMBINANT PROTEINS; STATISTICAL MECHANICS;

CHO CELL; NEXT-GENERATION SEQUENCING; POINT MUTATIONS; RECOMBINANT MONOCLONAL ANTIBODY; SEQUENCE VARIANTS;

CELLS;

CRICETULUS GRISEUS;

MESSENGER RNA; MONOCLONAL ANTIBODY; RECOMBINANT PROTEIN;

ANIMAL; CHEMISTRY; CHO CELL LINE; CRICETULUS; GENETICS; HAMSTER; METABOLISM; MUTATION; PROCEDURES; SEQUENCE ANALYSIS;

ANIMALS; ANTIBODIES, MONOCLONAL; CHO CELLS; CRICETINAE; CRICETULUS; MUTATION; RECOMBINANT PROTEINS; RNA, MESSENGER; SEQUENCE ANALYSIS, RNA;

EID: 84938982248     PISSN: 87567938     EISSN: 15206033     Source Type: Journal    
DOI: 10.1002/btpr.2119     Document Type: Article

References (44)

1. Wurm FM. Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol. 2004;22:1393-1398.
2. Li F, Vijayasankaran N, Shen AY, Kiss R, Amanullah A. Cell culture processes for monoclonal antibody production. MAbs. 2010;2:466-479.
3. Rosenberger RF. Translational effects. Biologicals. 1993;21:101.
4. Harris RJ, Murnane AA, Utter SL, et al. Assessing genetic heterogeneity in production cell lines: detection by peptide mapping of a low level Tyr to Gln sequence variant in a recombinant antibody. Biotechnology (N Y). 1993;11:1293-1297.
5. Ren D, Zhang J, Pritchett R, et al. Detection and identification of a serine to arginine sequence variant in a therapeutic monoclonal antibody. J Chromatogr B. 2011;879:2877-2884.
6. Dorai H, Sauerwald, T, Campbell A, et al. Investigation of product microheterogeneity: a case study in rapid detection of mutation in mammalian production cell lines. Bioprocess Int. 2007;5:66.
7. Zhang T, Huang Y, Chamberlain S, et al. Identification of a single base-pair mutation of TAA (Stop codon) -> GAA (Glu) that causes light chain extension in a CHO cell derived IgG1. MAbs. 2012;4.
8. Fu J, Bongers J, Tao L, et al. Characterization and identification of alanine to serine sequence variants in an IgG4 monoclonal antibody produced in mammalian cell lines. J Chromatogr B. 2012;908:1-8.
9. Yang Y, Strahan A, Li C, et al. Detecting low level sequence variants in recombinant monoclonal antibodies. MAbs. 2010;2:285-298.
10. Zeck A, Regula JT, Larraillet V, et al. Low level sequence variant analysis of recombinant proteins: an optimized approach. PloS One. 2012;7:e40328.
11. Manuilov AV, Radziejewski CH, Lee DH. Comparability analysis of protein therapeutics by bottom-up LC-MS with stable isotope-tagged reference standards. MAbs. 2011;3:387-395.
12. Yu XC, Borisov OV, Alvarez M, Michels DA, Wang YJ, Ling V. Identification of codon-specific serine to asparagine mistranslation in recombinant monoclonal antibodies by high-resolution mass spectrometry. Anal Chem. 2009;81:9282-9290.
13. Brady LJ, Scott RA, Balland A. An optimized approach to the rapid assessment and detection of sequence variants in recombinant protein products. Anal Bioanal Chem. 2015;407:3851-3860.
14. Zhang Z, Shah B, Bondarenko PV. G/U and certain wobble position mismatches as possible main causes of amino acid misincorporations. Biochemistry. 2013;52:8165-8176.
15. Liu J, Lee W, Jiang Z, et al. Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events. Genome Res. 2012;22:2315-2327.
16. Yee JC, Gerdtzen ZP, Hu WS. Comparative transcriptome analysis to unveil genes affecting recombinant protein productivity in mammalian cells. Biotechnol Bioeng. 2009;102:246-263.
17. Xu X, Nagarajan H, Lewis NE, et al. The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line. Nat Biotechnol. 2011;29:735-741.
18. Hammond S, Swanberg JC, Kaplarevic M, Lee KH. Genomic sequencing and analysis of a Chinese hamster ovary cell line using Illumina sequencing technology. BMC Genom. 2011;12:67.
19. Talkowski ME, Ordulu Z, Pillalamarri V, et al. Clinical diagnosis by whole-genome sequencing of a prenatal sample. N Engl J Med. 2012;367:2226-2232.
20. Welkers MR, Jonges M, Jeeninga RE, Koopmans MP, de Jong MD. Improved detection of artifactual viral minority variants in high-throughput sequencing data. Front Microbiol. 2014;5:804.
21. Victoria JG, Wang C, Jones MS, et al. Viral nucleic acids in live-attenuated vaccines: detection of minority variants and an adventitious virus. J Virol. 2010;84:6033-6040.
22. Bodwell J, Swiff F, Richardson J. Long duration electroporation for achieving high level expression of glucocorticoid receptors in mammalian cell lines. J Steroid Biochem Mol Biol. 1999;68:77-82.
23. Gion WR, Davis-Taber RA, Regier DA, et al. Expression of antibodies using single open reading frame (sORF) vector design: demonstration of manufacturing feasibility. MAbs. 2013;5:595-607.
24. Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10:R25.
25. Wen D, Vecchi MM, Gu S, et al. Discovery and investigation of misincorporation of serine at asparagine positions in recombinant proteins expressed in Chinese hamster ovary cells. J Biol Chem. 2009;284:32686-32694.
26. Feeney L, Carvalhal V, Yu XC, et al. Eliminating tyrosine sequence variants in CHO cell lines producing recombinant monoclonal antibodies. Biotechnol Bioeng. 2013;110:1087-1097.
27. Khetan A, Huang YM, Dolnikova J, et al. Control of misincorporation of serine for asparagine during antibody production using CHO cells. Biotechnol Bioeng. 2010;107:116-123.
28. Guo D, Gao A, Michels DA, et al. Mechanisms of unintended amino acid sequence changes in recombinant monoclonal antibodies expressed in Chinese Hamster Ovary (CHO) cells. Biotechnol Bioeng. 2010;107:163-171.
29. Lebkowski JS, DuBridge RB, Antell EA, Greisen KS, Calos MP. Transfected DNA is mutated in monkey, mouse, and human cells. Mol Cell Biol. 1984;4:1951-1960.
30. McCulloch SD, Kunkel TA. The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases. Cell Res. 2008;18:148-161.
31. Lewis NE, Liu X, Li Y, et al. Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome. Nat Biotechnol. 2013;31:759-765.
32. Miller JH, Lebkowski JS, Greisen KS, Calos MP. Specificity of mutations induced in transfected DNA by mammalian cells. EMBO J. 1984;3:3117-3121.
33. Goulian M, Bleile B, Tseng BY. Methotrexate-induced misincorporation of uracil into DNA. Proc Natl Acad Sci USA. 1980;77:1956-1960.
34. Martin SA, McCarthy A, Barber LJ, et al. Methotrexate induces oxidative DNA damage and is selectively lethal to tumour cells with defects in the DNA mismatch repair gene MSH2. EMBO Mol Med. 2009;1:323-337.
35. Chen F, Fan L, Wang J, et al. Insight into the roles of hypoxanthine and thymidine [corrected] on cultivating antibody-producing CHO cells: cell growth, antibody production and long-term stability. Appl Microbiol Biotechnol. 2012;93:169-178.
36. Liu J, Regier D, Zhang S, Carson G, Ouellette D. Methods of Selecting Biologic-Producing Cell Lines by Next Generation Sequencing. U.S. Patent Application Number 14/446, 653. 2014.
37. Metzker ML. Sequencing technologies-the next generation. Nat Rev Genet. 2010;11:31-46.
38. Maitra RD, Kim J, Dunbar WB. Recent advances in nanopore sequencing. Electrophoresis. 2012;33:3418-3428.
39. Rizzo JM, Buck MJ. Key principles and clinical applications of "next-generation" DNA sequencing. Cancer Prev Res (Phila). 2012;5:887-900.
40. Mestan KK, Ilkhanoff L, Mouli S, Lin S. Genomic sequencing in clinical trials. J. Transl. Med. 2011;9:222.
41. Horner DS, Pavesi G, Castrignano T, et al. Bioinformatics approaches for genomics and post genomics applications of next-generation sequencing. Brief. Bioinf. 2010;11:181-197.
42. Shokralla S, Spall JL, Gibson JF, Hajibabaei M. Next-generation sequencing technologies for environmental DNA research. Mol. Ecol. 2012;21:1794-1805.
43. Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009;10:57-63.
44. Popp O, Larraillet V, Kettenberger H, et al. Molecular polygamy: the promiscuity of l-phenylalanyl-tRNA-synthetase triggers misincorporation of meta- and ortho-tyrosine in monoclonal antibodies expressed by Chinese hamster ovary cells. Biotechnol Bioeng. 2015;112:1187-1199.