Review Article | Published:

Transgenic plants as factories for biopharmaceuticals

Nature Biotechnology volume 18, pages 11511155 (2000) | Download Citation

Subjects

Abstract

Plants have considerable potential for the production of biopharmaceutical proteins and peptides because they are easily transformed and provide a cheap source of protein. Several biotechnology companies are now actively developing, field testing, and patenting plant expression systems, while clinical trials are proceeding on the first biopharmaceuticals derived from them. One transgenic plant-derived biopharmaceutical, hirudin, is now being commercially produced in Canada for the first time. Product purification is potentially an expensive process, and various methods are currently being developed to overcome this problem, including oleosin-fusion technology, which allows extraction with oil bodies. In some cases, delivery of a biopharmaceutical product by direct ingestion of the modified plant potentially removes the need for purification. Such biopharmaceuticals and edible vaccines can be stored and distributed as seeds, tubers, or fruits, making immunization programs in developing countries cheaper and potentially easier to administer. Some of the most expensive biopharmaceuticals of restricted availability, such as glucocerebrosidase, could become much cheaper and more plentiful through production in transgenic plants.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & Plant expression systems for the production of vaccines. Curr. Topics Microbiol. Immunol. 236, 275–292 (1999).

  2. 2.

    et al. Expression of human blood proteins in transgenic plants: the cytokine GM-CSF as a model protein. In Transgenic plants: a production system for industrial and pharmaceutical proteins. (eds Owen, M.R.L. & Pen, J). 281–297 (John Wiley & Sons, London, UK; 1996).

  3. 3.

    Comparison of host systems for the production of recombinant proteins. In Transgenic plants: a production system for industrial and pharmaceutical proteins. (eds Owen, M.R.L. & Pen, J.) 149–167 (John Wiley & Sons, London, UK; 1996).

  4. 4.

    The production of recombinant proteins in plants. J. Sci. Food Agric. 68, 1–9 (1995).

  5. 5.

    “Molecular farming” in plants: achievements and prospects. Biotechnol. Eng. 9, 3–9 (1995).

  6. 6.

    et al. Production of biologically active hirudin in plant seeds using oleosin partitioning. Plant Mol. Biol. 29, 1167–1180 (1995).

  7. 7.

    , & Production of recombinant proteins in transgenic plants: practical considerations. Biotechnol. Bioeng. 56, 473–484 (1997).

  8. 8.

    & Antibody production and engineering in plants, In Engineering plants for commercial products and applications. (eds Collins, G.B. & Sheperd, R.J.) 72–81 (New York Academy of Sciences, NY; 1996).

  9. 9.

    & The production of antibodies in plants. Biotechnol. Adv. 18, 85–89 (2000).

  10. 10.

    et al. N-glycosylation of a mouse IgG expressed in transgenic tobacco plants. Glycobiology 9, 365–372 (1999).

  11. 11.

    , , & High-level and stable accumulation of single-chain Fv antibodies in plant storage organs. J. Plant Physiol. 152, 708–711 (1998).

  12. 12.

    et al. Production of correctly processed human serum albumin in transgenic plants. Bio/Technology 8, 217–221 (1990).

  13. 13.

    et al. Bioproduction of human enzymes in transgenic tobacco. In Engineering plants for commercial products and applications. (eds Collins, G.B. & Sheperd, R.J.) 62–71 (New York Academy Of Sciences, NY; 1996).

  14. 14.

    Foreign protein production in plant tissue cultures Curr. Opin. Biotechnol. 11, 199–204 (2000).

  15. 15.

    & A review of oral vaccination with transgenic vegetables. Microbes Infect. 1, 777–783 (1999).

  16. 16.

    & Production of novel compounds in higher plants by transfection with RNA viral vectors. In Engineering plants for commercial products and applications. (eds Collins, G.B. & Sheperd, R.J.) 57–61 (New York Academy of Sciences, NY; 1996).

  17. 17.

    , & Production of antibodies in transgenic plants. Nature 342, 76–78 (1989).

  18. 18.

    et al. Rapid, high-level expression of biologically active alpha-trichosanthin in transfected plants by an RNA viral vector. Proc. Natl. Acad. Sci. USA 90, 427–430 (1993).

  19. 19.

    et al. Rapid production of specific vaccines for lymphoma by expression of the tumor-derived single-chain Fv epitopes in tobacco plants. Proc. Natl. Acad. Sci. USA 96, 703–708 (1999).

  20. 20.

    , & Molecular farming in plants: oilseeds as vehicles for the production of pharmaceutical proteins. Drug Develop. Res. 42, 172–181 (1997).

  21. 21.

    et al. A new tobacco mosaic virus vector and its use for the systematic production of angiotensin-I-converting enzyme inhibitor in transgenic tobacco and tomato. Bio/Technology 11, 930–932 (1993).

  22. 22.

    et al. Expression of the rabies virus glycoprotein in transgenic tomatoes. Bio/Technology 13, 1484–1487 (1995).

  23. 23.

    Edible plant vaccines. Nat. Biotechnol. 14,1532–1533 (1996).

  24. 24.

    et al. Plant-derived vaccine protects target animals against a viral disease. Nat. Biotechnol. 15, 248–252 (1997).

  25. 25.

    & Plants as bioreactors. Trends Biotechnol. 13, 379–387 (1995).

  26. 26.

    et al. Enkephalines produced in transgenic plants using modified 2S storage proteins. Bio/Technology 7, 929–932 (1989).

  27. 27.

    , & Transgenic Brassica carinata as a vehicle for the production of recombinant proteins in seeds. Plant Cell Reports 17,195–200 (1998).

  28. 28.

    et al. Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato. Nat. Med. 4, 607–609 (1998).

  29. 29.

    et al. Transgenic plants expressing autoantigens fed to induce oral immune tolerance. Nat. Med. 3, 793–517 (1997).

  30. 30.

    & Transgenic plant technology is entering the era of metabolic engineering. Trends Biotechnol. 15, 441–444 (1997).

  31. 31.

    et al. Potato tubers as a biofactory for recombinant antibodies. Mol. Breeding 4, 313–319 (1998).

  32. 32.

    et al. Transgenic rice (Oryza sativa) endosperm expressing daffodil (Narcissus pseudonarcissus) phytoene synthase accumulates phytoene, a key intermediate of provitamin a biosynthesis. Plant J. 11, 1071–1078 (1997).

  33. 33.

    et al. Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies. Plant Mol. Biol. 42, 583–590 (2000).

  34. 34.

    et al. Commercial production of aprotinin in transgenic maize seeds. Mol. Breeding 5, 345–356 (1999).

  35. 35.

    & Genetic elements of plant viruses as tools for genetic engineering. Microbiol. Rev. 59, 548–578 (1995).

  36. 36.

    , & Use of plant viruses for delivery of vaccine epitopes, In Engineering plants for commercial products and applications. (eds Collins, G.B. & Sheperd, R.J.) 43–49 (New York Academy of Sciences, NY; 1996).

  37. 37.

    et al. Malarial epitopes expressed on the surface of recombinant tobacco mosaic virus. Bio/Technology 13, 53–57 (1995).

  38. 38.

    et al. Chimeric plant virus particles administered nasally or orally induce systemic and mucosal immune responses in mice. J. Virol. 73, 930–938 (1999).

  39. 39.

    et al. Intranasal immunization with a plant virus expressing a peptide from HIV-1 gp41 stimulates better mucosal and systemic HIV-1-specific IgA and IgG than oral immunization. J. Immunol. Methods 220, 93–103 (1998).

  40. 40.

    & Expressing antibodies in plants for immunotherapy. In Transgenic plants: a production system for industrial and pharmaceutical proteins. (eds Owen, M.R.L. & Pen, P.) 229–243 (John Wiley & Sons, London, UK; 1996).

  41. 41.

    , & Transgenic plants for therapeutic proteins: linking upstream and downstream strategies. Curr. Topics Microbiol. Immunol. 240, 95–118 (1999).

  42. 42.

    & Plant-based production of xenogenic proteins. Curr. Opin. Biotechnol. 10, 382–386 (1999).

  43. 43.

    et al. Immunogenicity of transgenic plant-derived hepatitis B surface antigen. Proc. Natl. Acad. Sci. USA 92, 3358–3361 (1995).

  44. 44.

    , Anti-viral vaccines expressed in plants. US 05612487 (1997); Arntzen, C.J. & Lam, D.M-K. Vaccines expressed in plants. US 5914123 (1995); Arntzen, C.J. & Lam, D.M-K. Vaccines produced and administered through edible plants. US 5484719 (1996); Arntzen, C.J., Lam, D.M-K, Mason, H.S. Vaccines expressed in plants. US 6034298 (2000).

  45. 45.

    , , & Production of hepatitis B surface antigen in transgenic plants for oral immunization. Nat. Biotechnol. 18, 1167–1171 (2000).

  46. 46.

    et al. A plant-based cholera toxin B subunit-insulin fusion protein protects against the development of autoimmune diabetes. Nat. Biotechnol. 16, 934–938 (1998).

  47. 47.

    , & Efficacy of a food plant-based oral cholera toxin B subunit vaccine. Nat. Biotechnol. 16, 292–297 (1998).

  48. 48.

    et al. Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat. Med. 4, 1078–8956 (1998).

  49. 49.

    , , & Antibody production by molecular farming in plants. J. Biol. Regul. Homeost. Agents 14, 83–92 (2000).

  50. 50.

    et al. Occurrence, fate and effects of pharmaceutical substances in the environment–a review. Chemosphere 36, 357–394 (1998).

  51. 51.

    et al. Human haemoglobin from transgenic tobacco. Nature 386, 29–30 (1997).

  52. 52.

    et al. Triple helix assembly and processing of human collagen produced in transgenic tobacco plants. FEBS Lett. 469, 132–136 (2000).

  53. 53.

    , , & Increased nutritive value of transgenic potato by expressing a nonallergenic seed albumin gene from Amaranthus hypochondriacus. Proc. Natl. Acad. Sci. USA 97, 3724–2729 (2000).

  54. 54.

    & Reducing transgene escape routes. Nature 392, 653–654 (1998).

Download references

Acknowledgements

Our thanks to the UK Department of Transport, Environment and the Regions (DETR), who funded this work as part of their program on risk assessment for the release of genetically modified plants.

Author information

Affiliations

  1. Institute of Biological Sciences, University of Wales, Aberystwyth, Cledwyn Building, Aberystwyth Ceredigion SY23 3DD, UK.

    • Glynis Giddings
    • , Gordon Allison
    • , Douglas Brooks
    •  & Adrian Carter

Authors

  1. Search for Glynis Giddings in:

  2. Search for Gordon Allison in:

  3. Search for Douglas Brooks in:

  4. Search for Adrian Carter in:

Corresponding author

Correspondence to Glynis Giddings.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/81132

Further reading