Skip to main content
SpringerLink
Log in

Production of Antibody by Transgenic Avians

  • Chapter
  • First Online:
Antibody Expression and Production

Part of the book series: Cell Engineering ((CEEN,volume 7))

Abstract

Transgenic avian bioreactors are being proposed as a powerful way of addressing the growing need for recombinant biopharmaceutical production. Avian systems as transgenic bioreactors have several advantages including high protein productivity in eggs, a relatively short period of sexual maturation, and similar protein glycosylation patterns to those of humans. Several examples of successful viral biopharmaceuticals are already being produced as human vaccines. In this chapter, we describe the generation of genetically manipulated (GM) avians producing pharmaceutical proteins including antibodies using retroviral vectors for gene transfer, the analysis of glycosylation patterns of recombinant antibodies produced in the serum and eggs of GM chickens, and the recovery of recombinant antibodies and Fc-fusion proteins mediated by yolk transport. The development of transgenic avian bioreactors promises to be an important procedure for production of therapeutic proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Bae HD, Kobayashi M, Horio F, Murai A (2010) Identification of the amino acid residues involved in human IgG transport into egg yolks of Japanese quail (Coturnix japonica). Mol Immunol 47:1404–1410.

    Article  PubMed  CAS  Google Scholar 

  • Burns JC, Friedmann T, Driever W, Burrascano M, Yee JK (1993) Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells. Proc Natl Acad Sci USA 90:8033–8037.

    Article  PubMed  CAS  Google Scholar 

  • Clackson T, Hoogenboom HR, Griffiths AD, Winter G (1991) Making antibody fragments using phage display libraries. Nature 352:624–628.

    Article  PubMed  CAS  Google Scholar 

  • Dyck MK, Lacroix D, Pothier F, Sirard MA (2003) Making recombinant proteins in animals-different systems, different applications. Trends Biotechnol 21:394–399.

    Article  PubMed  CAS  Google Scholar 

  • Enever C, Batuwangala T, Plummer C, Sepp A (2009) Next generation immunotherapeutics–honing the magic bullet. Curr Opin Biotechnol 20:405–411.

    Article  PubMed  CAS  Google Scholar 

  • Hamburger V, Hamilton HL (1951) A series of normal stages in the development of the chick embryo. J Morphol 88:49–92.

    Article  Google Scholar 

  • Harel-Markowitz E, Gurevich M, Shore LS, Katz A, Stram Y, Shemesh M (2009) Use of sperm plasmid DNA lipofection combined with REMI (restriction enzyme-mediated insertion) for production of transgenic chickens expressing eGFP (enhanced green fluorescent protein) or human follicle-stimulating hormone. Biol Reprod 80:1046–1052.

    Article  PubMed  CAS  Google Scholar 

  • Harvey AJ, Speksnijder G, Baugh LR, Morris JA, Ivarie R (2002) Expression of exogenous protein in the egg white of transgenic chickens. Nat Biotechnol 20:396–399.

    Article  PubMed  CAS  Google Scholar 

  • Hotta A, Kamihira M, Itoh K, Morshed M, Kawabe Y, Ono K, Matsumoto H, Nishijima K, Iijima S (2004) Production of anti-CD2 chimeric antibody by recombinant animal cells. J Biosci Bioeng 98:298–303.

    PubMed  CAS  Google Scholar 

  • Houdebine LM (2009) Production of pharmaceutical proteins by transgenic animals. Comp Immunol Microbiol Infect Dis 32:107–121.

    Article  PubMed  Google Scholar 

  • Ivarie R (2003) Avian transgenesis: progress towards the promise. Trends Biotechnol 21:14–19.

    Article  PubMed  CAS  Google Scholar 

  • Kamihira M, Kawabe Y, Shindo T, Ono K, Esaka K, Yamashita T, Nishijima K, Iijima S (2009) Production of chimeric monoclonal antibodies by genetically manipulated chickens. J Biotechnol 141:18–25.

    Article  PubMed  CAS  Google Scholar 

  • Kamihira M, Ono K, Esaka K, Nishijima K, Kigaku R, Komatsu H, Yamashita T, Kyogoku K, Iijima S (2005) High-level expression of single-chain Fv-Fc fusion protein in serum and egg white of genetically manipulated chickens by using a retroviral vector. J Virol 79:10864–10874.

    Article  PubMed  CAS  Google Scholar 

  • Kawabe Y, Kamihira M, Ono K, Kyogoku K, Nishijima K, Iijima S (2006a) Production of scFv-Fc fusion protein using genetically manipulated quails. J Biosci Bioeng 102:297–303.

    Article  PubMed  CAS  Google Scholar 

  • Kawabe Y, Naka T, Ando-Noumi N, Matsumoto H, Ono K, Nishijima K, Kamihira M, Iijima S (2006b) Transport of human immunoglobulin G and Fc-fusion proteins to chicken egg yolk. J Biosci Bioeng 102:518–523.

    Article  PubMed  CAS  Google Scholar 

  • Kawabe Y, Naka T, Komatsu H, Nishijima K, Iijima S, Kamihira M (2008) Retroviral gene transduction into chicken embryo gonads through blood circulation. J Biosci Bioeng 106:598–601.

    Article  PubMed  CAS  Google Scholar 

  • Kitaguchi K, Osada K, Horio F, Murai A (2008) Exclusion of polymeric immunoglobulins and selective immunoglobulin Y transport that recognizes its Fc region in avian ovarian follicles. Vet Immunol Immunopathol 121:290–299.

    Article  PubMed  CAS  Google Scholar 

  • Kodama D, Nishimiya D, Iwata K, Yamaguchi K, Yoshida K, Kawabe Y, Motono M, Watanabe H, Yamashita T, Nishijima K, Kamihira M, Iijima S (2008) Production of human erythropoietin by chimeric chickens. Biochem Biophys Res Commun 367:834–839.

    Article  PubMed  CAS  Google Scholar 

  • Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497.

    Article  PubMed  Google Scholar 

  • Köhler G (1980) Immunoglobulin chain loss in hybridoma lines. Proc Natl Acad Sci USA 77:2197–2199.

    Article  PubMed  Google Scholar 

  • Koo BC, Kwon MS, Lee H, Kim M, Kim D, Roh JY, Park YY, Cui XS, Kim NH, Byun SJ, Kim T (2010) Tetracycline-dependent expression of the human erythropoietin gene in transgenic chickens. Transgenic Res 19:437–447.

    Article  PubMed  CAS  Google Scholar 

  • Kues WA, Niemann H (2004) The contribution of farm animals to human health. Trends Biotechnol 22:286–294.

    Article  PubMed  CAS  Google Scholar 

  • Kuwana T (1993) Migration of avian primordial germ cells toward the gonadal anlage. Dev Growth Differ 35:237–243.

    Article  Google Scholar 

  • Kwon SC, Choi JW, Jang HJ, Shin SS, Lee SK, Park TS, Choi IY, Lee GS, Song G, Han JY (2010) Production of biofunctional recombinant human interleukin 1 receptor antagonist (rhIL1RN) from transgenic quail egg white. Biol Reprod 82:1057–1064.

    Article  PubMed  CAS  Google Scholar 

  • Kwon MS, Koo BC, Choi BR, Park YY, Lee YM, Suh HS, Park YS, Lee HT, Kim JH, Roh JY, Kim NH, Kim T (2008) Generation of transgenic chickens that produce bioactive human granulocyte-colony stimulating factor. Mol Reprod Dev 75:1120–1126.

    Article  PubMed  CAS  Google Scholar 

  • Kyogoku K, Yoshida K, Watanabe H, Yamashita T, Kawabe Y, Motono M, Nishijima K, Kamihira M, Iijima S (2008) Production of recombinant tumor necrosis factor receptor/Fc fusion protein by genetically manipulated chickens. J Biosci Bioeng 105:454–459.

    Article  PubMed  CAS  Google Scholar 

  • Lavial F, Pain B (2010) Chicken embryonic stem cells as a non-mammalian embryonic stem cell model. Dev Growth Differ 52:101–114.

    Article  PubMed  CAS  Google Scholar 

  • Lavine G (2009) FDA approves first biological product derived from transgenic animal. Am J Health Syst Pharm 66:518.

    Article  PubMed  Google Scholar 

  • Lee SH, Gupta MK, Han DW, Han SY, Uhm SJ, Kim T, Lee HT (2007) Development of transgenic chickens expressing human parathormone under the control of a ubiquitous promoter by using a retrovirus vector system. Poult Sci 86:2221–2227.

    PubMed  CAS  Google Scholar 

  • Lillico SG, McGrew MJ, Sherman A, Sang HM (2005) Transgenic chickens as bioreactors for protein-based drugs. Drug Discov Today 10:191–196.

    Article  PubMed  CAS  Google Scholar 

  • Lillico SG, Sherman A, McGrew MJ, Robertson CD, Smith J, Haslam C, Barnard P, Radcliffe PA, Mitrophanous KA, Elliot EA, Sang HM (2007) Oviduct-specific expression of two therapeutic proteins in transgenic hens. Proc Natl Acad Sci USA 104:1771–1776.

    Article  PubMed  CAS  Google Scholar 

  • Loeken MR, Roth TF (1983) Analysis of maternal IgG subpopulations which are transported into the chicken oocyte. Immunology 49:21–28.

    PubMed  CAS  Google Scholar 

  • Love J, Gribbin C, Mather C, Sang H (1994) Transgenic birds by DNA microinjection. Biotechnology 12:60–63.

    Article  PubMed  CAS  Google Scholar 

  • Massoud M, Attal J, Thépot D, Pointu H, Stinnakre MG, Théron MC, Lopez C, Houdebine LM (1996) The deleterious effects of human erythropoietin gene driven by the rabbit whey acidic protein gene promoter in transgenic rabbits. Reprod Nutr Dev 36:555–563.

    Article  PubMed  CAS  Google Scholar 

  • McGrew MJ, Sherman A, Ellard FM, Lillico SG, Gilhooley HJ, Kingsman AJ, Mitrophanous KA, Sang H (2004) Efficient production of germline transgenic chickens using lentiviral vectors. EMBO Rep 5:728–733.

    Article  PubMed  CAS  Google Scholar 

  • Mizuarai S, Ono K, Yamaguchi K, Nishijima K, Kamihira M, Iijima S (2001) Production of transgenic quails with high frequency of germ-line transmission using VSV-G pseudotyped retroviral vector. Biochem Biophys Res Commun 286:456–463.

    Article  PubMed  CAS  Google Scholar 

  • Mizuguchi H, Xu Z, Ishii-Watabe A, Uchida E, Hayakawa T (2000) IRES-dependent second gene expression is significantly lower than cap-dependent first gene expression in a bicistronic vector. Mol Ther 1:376–382.

    Article  PubMed  CAS  Google Scholar 

  • Mohammed SM, Morrison S, Wims L, Trinh KR, Wildeman AG, Bonselaar J, Etches RJ (1998) Deposition of genetically engineered human antibodies into the egg yolk of hens. Immunotechnology 4:115–125.

    Article  PubMed  CAS  Google Scholar 

  • Morrison SL, Mohammed MS, Wims LA, Trinh R, Etches R (2002) Sequences in antibody molecules important for receptor-mediated transport into the chicken egg yolk. Mol Immunol 38:619–625.

    Article  PubMed  CAS  Google Scholar 

  • Mozdziak PE, Borwornpinyo S, McCoy DW, Petitte JN (2003) Development of transgenic chickens expressing bacterial β-galactosidase. Dev Dyn 226:439–445.

    Article  PubMed  CAS  Google Scholar 

  • Murray KM, Dahl SL (1997) Recombinant human tumor necrosis factor receptor (p75) Fc fusion protein (TNFR:Fc) in rheumatoid arthritis. Ann Pharmacother 31:1335–1338.

    PubMed  CAS  Google Scholar 

  • Penno CA, Kawabe Y, Ito A, Kamihira M (2010) Production of recombinant human erythropoietin/Fc fusion protein by genetically manipulated chickens. Transgenic Res 19:187–195.

    Article  PubMed  CAS  Google Scholar 

  • Pollock DP, Kutzko JP, Birck-Wilson E, Williams JL, Echelard Y, Meade HM (1999) Transgenic milk as a method for the production of recombinant antibodies. J Immunol Methods 231:147–157.

    Article  PubMed  CAS  Google Scholar 

  • Raju TS, Briggs JB, Borge SM, Jones AJ (2000) Species-specific variation in glycosylation of IgG: evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics. Glycobiology 10:477–486.

    Article  PubMed  CAS  Google Scholar 

  • Rapp JC, Harvey AJ, Speksnijder GL, Hu W, Ivarie R (2003) Biologically active human interferon alpha-2b produced in the egg white of transgenic hens. Transgenic Res 12:569–575.

    Article  PubMed  CAS  Google Scholar 

  • Reichert JM, Valge-Archer VE (2007) Development trends for monoclonal antibody cancer therapeutics. Nat Rev Drug Discov 6:349–356.

    Article  PubMed  CAS  Google Scholar 

  • Robertson G, Garrick D, Wu W, Kearns M, Martin D, Whitelaw E (1995) Position-dependent variegation of globin transgene expression in mice. Proc Natl Acad Sci USA 92:5371–5375.

    Article  PubMed  CAS  Google Scholar 

  • Sang H (2004) Prospects for transgenesis in the chick. Mech Dev 121:1179–1186.

    Article  PubMed  CAS  Google Scholar 

  • Sherman A, Dawson A, Mather C, Gilhooley H, Li Y, Mitchell R, Finnegan D, Sang H (1998) Transposition of the Drosophila element mariner into the chicken germ line. Nat Biotechnol 16:1050–1053.

    Article  PubMed  CAS  Google Scholar 

  • Shukla AA, Thömmes J (2010) Recent advances in large-scale production of monoclonal antibodies and related proteins. Trends Biotechnol 28:253–261.

    Article  PubMed  CAS  Google Scholar 

  • Song G, Park TS, Kim TM, Han JY (2010) Avian biotechnology: insights from germ cell-mediated transgenic systems. J Poult Sci 47:197–207.

    Article  Google Scholar 

  • Steurer W, Nickerson PW, Steele AW, Steiger J, Zheng XX, Strom TB (1995) Ex vivo coating of islet cell allografts with murine CTLA4/Fc promotes graft tolerance. J Immunol 155:1165–1174.

    PubMed  CAS  Google Scholar 

  • Tajima A, Hayashi H, Kamizumi A, Ogura J, Kuwana T, Chikamune T (1999) Study on the concentration of circulating primordial germ cells (cPGCs) in early chick embryos. J Exp Zool 284:759–764.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi N, Ishii I, Ishihara H, Mori M, Tejima S, Jefferis R, Endo S, Arata Y (1987) Comparative structural study of the N-linked oligosaccharides of human normal and pathological immunoglobulin G. Biochemistry 26:1137–1144.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676.

    Article  PubMed  CAS  Google Scholar 

  • Tsumoto K, Shinoki K, Kondo H, Uchikawa M, Juji T, Kumagai I (1998) Highly efficient recovery of functional single-chain Fv fragments from inclusion bodies overexpressed in Escherichia coli by controlled introduction of oxidizing reagent – application to a human single-chain Fv fragment. J Immunol Methods 219:119–129.

    Article  PubMed  CAS  Google Scholar 

  • van de Lavoir MC, Diamond JH, Leighton PA, Mather-Love C, Heyer BS, Bradshaw R, Kerchner A, Hooi LT, Gessaro TM, Swanberg SE, Delany ME, Etches RJ (2006) Germline transmission of genetically modified primordial germ cells. Nature 441:766–769.

    Article  PubMed  Google Scholar 

  • Wheeler MB (2007) Agricultural applications for transgenic livestock. Trends Biotechnol 25:204–210.

    Article  PubMed  CAS  Google Scholar 

  • Whitelaw CB (2004) Transgenic livestock made easy. Trends Biotechnol 22:157–159.

    Article  PubMed  CAS  Google Scholar 

  • Wilson C, Bellen HJ, Gehring WJ (1990) Position effects on eukaryotic gene expression. Annu Rev Cell Biol 6:679–714.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Yu F, Ding LJ, Sun GB, Sun PX, He XH, Ni LG, Li BC (2010) Transgenic sperm produced by electrotransfection and allogeneic transplantation of chicken fetal spermatogonial stem cells. Mol Reprod Dev 77:340–347.

    PubMed  CAS  Google Scholar 

  • Zhu L, van de Lavoir MC, Albanese J, Beenhouwer DO, Cardarelli PM, Cuison S, Deng DF, Deshpande S, Diamond JH, Green L et al. (2005) Production of human monoclonal antibody in eggs of chimeric chickens. Nat Biotechnol 23:1159–1169.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported in part by Grant-in Aid for Scientific Research (no. 20360376) from the Japan Society for the Promotion of Science (JSPS).

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, Faculty of Engineering, Kyushu University, Fukuoka, 819-0395, Japan

    Yoshinori Kawabe & Masamichi Kamihira

Authors
  1. Yoshinori Kawabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masamichi Kamihira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masamichi Kamihira .

Editor information

Editors and Affiliations

  1. Dept. Chemical & Biochemical, Engineering, University College, Dublin, Belfield, Dublin 4, Ireland

    Mohamed Al-Rubeai

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Kawabe, Y., Kamihira, M. (2011). Production of Antibody by Transgenic Avians. In: Al-Rubeai, M. (eds) Antibody Expression and Production. Cell Engineering, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1257-7_6

Download citation

Publish with us

Policies and ethics

Search

Navigation