Plant Molecular Biology

, Volume 50, Issue 6, pp 837–854 | Cite as

Phage display: practicalities and prospects

  • William G.T. Willats

Abstract

Phage display is a molecular technique by which foreign proteins are expressed at the surface of phage particles. Such phage thereby become vehicles for expression that not only carry within them the nucleotide sequence encoding expressed proteins, but also have the capacity to replicate. Using phage display vast numbers of variant nucleotide sequences may be converted into populations of variant peptides and proteins which may be screened for desired properties. It is now some seventeen years since the first demonstration of the feasibility of this technology and the intervening years have seen an explosion in its applications. This review discusses the major uses of phage display including its use for elucidating protein interactions, molecular evolution and for the production of recombinant antibodies.

antibody microarrays immunomodulation molecular evolution Phage display protein interactions recombinant antibodies 

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References

  1. Casey, J.L., Coley, A.M., Tilley, L.M. and Foley, M. 2000. Green fluorescent antibodies: novel in vitro tools. Protein Engin. 13(6): 445–452.Google Scholar
  2. Castillo, J., Goodson, B. and Winter, J. 2001. T7 displayed peptides as targets for selecting peptide specific scFvs from M13 scFv display libraries. J. Immunol. Meth. 257: 117–122.Google Scholar
  3. Choo, Y., Sánchez-Garcia, I. and Klug, A. 1994. In vivo repression by a site-specific DNA-binding protein designed against an oncogenic sequence. Nature 372: 642–645.Google Scholar
  4. Clackson, T., Hoogenboom, H.R., Griffiths, A.D. and Winter, G. 1991. Making antibody fragments using phage display libraries. Nature 352: 624–628.Google Scholar
  5. Danielsen, S., Eklund, M., Deussen, H-J., Graslund, T., Nygren, P-Å. and Borchert, T.V. 2001. In vitro selection of enzymatically active lipase variants from phage libraries using a mechanismbased inhibitor. Gene 272: 267–274.Google Scholar
  6. Danner, S. and Belasco, J.G. 2001. T7 phage display: a novel genetic selection system for cloning RNA-binding proteins from cDNA libraries. Proc. Nat. Acad. Sci. USA 98(23): 12954–12959.Google Scholar
  7. Debouck, C. and Goodfellow, P.N. 1999. DNA microarrays in drug discovery and development. Nature Genetics (supplement) 21: 48–50.Google Scholar
  8. De Jaeger, C., De Wilde, C., Eeckhout, D., Fiers, E. and Depicker, A. 2000. The plantibody approach: expression of antibody genes in plants to modulate plant metabolism or to obtain pathogen resistance. Plant Mol. Biol. 43: 419–428.Google Scholar
  9. Dennis, M.S. and Lazarus, R.A. 1994. Kunitz domain inhibitors of tissue-factor VIIa. I. Potent inhibitors selected from libraries by phage display. J. Biol. Chem. 269: 22129–22136.Google Scholar
  10. Drees, B.L. 1999. Progress and variations in two-hybrid and three hybrid technologies. Curr. Opin. Chem. Biol. 3: 64–70.Google Scholar
  11. Gadella, T.W.J., van der Krogt, G. N. M. and Bisseling, T. 1999. GFP-based FRET microscopy in living plant cells. Trends Plant Sci. 4(7): 287–291.Google Scholar
  12. Griffiths, A.D., Malmqvist, M., Marks, J.D., Bye, J.M., Embleton, M.J., McCafferty, J., Baier, M., Holliger, K.P., Gorick, B.D., Hughes-Jones, N.C., Hoogenboom, H.R. and Winter, G. 1993. Human anti-self antibodies with high specificity from phage display libraries. EMBO J. 12(2): 725–734.Google Scholar
  13. Haab, B.B., Dunham, M.J. and Brown, P.O. 2001. Protein microarrays for highly parallel detection and quantification of specific proteins and antibodies in complex solutions. Genome Biol. 2(2): 1004.1–1004.13.Google Scholar
  14. Hamers-Casterman, C., Atarhouch, T., Muyldermans, S., Robinson, G., Memaers, C., Bajyana Songa, E., Bendahman, N. and Hamers, R. 1993. Naturally occurring antibodies devoid of light chains. Nature 363: 446–448.Google Scholar
  15. Hoogenboom, H.R. 1997. Designing and optimising library selection strategies for generating high-affinity antibodies. TIBTECH 15: 62–70.Google Scholar
  16. Hoogenboom, H.R., de Bruïne A.P., Hufton, S.E., Hoet, R.M., Arends, J-W. and Roovers, R.C. 1998. Antibody phage display and its applications. Immunotechnology 4: 1–20.Google Scholar
  17. Hoogenboom, H.R. and Winter, G. 1992. By-passing immunisation. Human antibodies from synthetic repertoires of germline VH segments rearranged in vitro. J. Mol. Biol. 227: 381–388.Google Scholar
  18. Johns, M., George, A.J.T. and Ritter, M.A. 2000. In vivo selection of scFv from phage display libraries. J. Immunol. Meth. 239: 137–151.Google Scholar
  19. Kay, B.K. and Hoess, R.H. 1996. Principles and applications of phage display. In: B.K. Kay, J. Winter and J. McCafferty (eds.) Phage display of peptides and proteins, Academic Press, pp. 21–34.Google Scholar
  20. Kay, B.K., Kasanov, J., Knight, S. and Kurakin, A. 2000. Convergent evolution with combinatorial peptides. FEBS Lett. 480: 55–62.Google Scholar
  21. Kirkham, P.M., Neri, D. and Winter, G. 1999. Towards the design of an antibody that recognises a given protein epitope. J. Mol. Biol. 285: 909–915.Google Scholar
  22. Kodadek, T. 2001. Protein microarrays: Prospects and problems. Chem. Biol. 8: 105–115.Google Scholar
  23. Lander, E.S. 1999. Array of hope. Nature Genetics (supplement) 21: 3–4.Google Scholar
  24. Lowman, H.B. and Wells, J.A. 1993. Affinity maturation of human growth hormone by monovalent phage display. J. Mol. Biol. 234: 564–578.Google Scholar
  25. Morino, K., Katsumi, H., Akahori, Y., Iba, Y., Shinohara, M., Ukai, Y., Kohara, Y. and Kurosawa, Y. 2001. Antibody fusions with fluorescent proteins: a versatile reagent for profiling protein expression. J. Immunol. Meth. 257: 175–184.Google Scholar
  26. Marks, J.D., Hoogenboom, H.R., Bonnert, T.P., McCafferty, J., Griffiths, A.D. and Winter, G. 1991. By-passing immunisation. Human antibodies from V-gene libraries displayed on phage. J. Mol. Biol. 222: 581–597.Google Scholar
  27. Matthews, D.J. 1996. Substrate phage. In: B.K. Kay, J. Winter and J. McCafferty (eds.), Phage display of peptides and proteins, Academic Press, pp. 255-259.Google Scholar
  28. Mendelsohn, A.R. and Brent, R. 1999. Protein interaction methods-towards an endgame. Science 18(284): 1948–1950.Google Scholar
  29. McCafferty, J. 1996. Phage display: factors affecting panning effi-ciency. In: B.K. Kay, J. Winter and J. McCafferty (eds.), Phage display of peptides and proteins, Academic Press, pp. 261-276.Google Scholar
  30. McCafferty, J. and Johnson, K.S. 1996. Construction and screening of antibody display libraries. In: B.K. Kay, J. Winter and J. McCafferty (eds.), Phage display of peptides and proteins, Academic Press, pp. 79-111.Google Scholar
  31. McPherson, M.J. and Harrison, D.J. 2001. Protease inhibitors and directed evolution: enhancing plant resistance to nematodes. In: A. Berry and S.E. Radford (eds.), From protein folding to new enzymes, Cambridge University Press, Cambridge, U.K.Google Scholar
  32. Nissim, A., Hoogenboom, H.R., Tomlinson, I.A., Flynn, G., Midgley, C., Lane, D. and Winter, G. 1994. Antibody fragments from a 'single-pot' phage display library as immunological reagents. EMBO J. 13: 692–697.Google Scholar
  33. Owen, M., Gandecha, A., Cockburn, B. and Whitelam, G. 1992. Synthesis of a functional anti-phytochrome single-chainFv protein in transgenic tobacco. Bio/technology 10: 790–794.Google Scholar
  34. Petrenko, V.A. and Smith, G.P. 2000. Phages from landscape libraries as substitutes for antibodies. Protein Engin. 13(8): 589–592.Google Scholar
  35. Rodi, D.J. and Makowski, L. 1999. Phage-display technology-finding a needle in a vast molecular haystack. Curr. Opin. Biotechnol. 10: 87–93.Google Scholar
  36. Rodi, D.J., Makowski, L. and Kay, B.K. 2001. One from column A and two from column B: the benefits of phage display in molecular-recognition studies. Curr. Opin. Chem. Biol. 6: 92–96.Google Scholar
  37. Rondot, S., Koch, J., Breitling, F. and Dübel, S. 2001. A helper phage to improve single-chain antibody presentation in phage display. Nature Biotechnol. 19: 75–78.Google Scholar
  38. Sidhu, S.S. 2001. Engineering M13 for phage display. Biomol. Engin. 18: 57–63.Google Scholar
  39. Shimada, N., Suzuki, Y., Nakajima, M., Conrad, U., Murofushi, N. and Yamaguchi, I. 1999. Expression of a functional singlechain antibody against GA24/19 in transgenic tobacco. Biosci. Biotechnol. Biochem. 63: 779–783.Google Scholar
  40. Shinohara, N., Demura, T. and Fukuda, H. 2000. Isolation of a vascular cell wall-specific monoclonal antibody recognising a cell polarity by using a phage display subtraction method. Proc. Nat. Acad. Sci. USA 97(5): 2585–2590.Google Scholar
  41. Smith, G.P. 1985. Filamentous phage fusion: novel expression vectors that display cloned antigens on the surface of the viron. Science 228: 1315–1317.Google Scholar
  42. Smith, M.D. and Glick, B.R. 2000. The production of antibodies in plants: an idea whose time has come? Biotechnol. Adv. 18: 85–89.Google Scholar
  43. Sparks, A.B., Adey, N.B., Cwirla, S. and Kay, B.K. 1996. Screening phage-displayed random peptide libraries. In: B.K. Kay, J. Winter and J. McCafferty (eds.), Phage display of peptides and proteins, Academic Press, pp. 227-253.Google Scholar
  44. Strauß M., Kauder, F., Peisker, M., Sonnewald, U., Conrad, U. and Heineke, D. 2001. Expression of an abscisic acid-binding single-chain antibody influences the subcellular distribution of abscisic acid and leads to developmental changes in transgenic potato plants. Planta 213: 361–369.Google Scholar
  45. Tomlinson, I.M. and Holt, L.J. 2001. Protein profiling cones of age. Genome Biol. 2(2): 1004.1–1004.3.Google Scholar
  46. Truong, K. and Ikura, M. 2001. The use of FRET imaging microscopy to detect protein-protein interactions and protein conformational changes in vivo. Curr. Opin. Struct. Biol. 11: 573–578.Google Scholar
  47. Watters, J.M., Telleman, P. and Junghans, R.P. 1997. An optimised method for cell based phage display panning. Immunotechnology 3: 21–29.Google Scholar
  48. Whaley, S.R., English, D.S., Hu, E.L., Barbara, P.F. and Belcher, A.M. 2000. Selection of peptides with semiconductor binding specificity for directed nanocrystal assembly. Nature 405: 665–668.Google Scholar
  49. Willats, W.G.T., Gilmartin, P.M., Mikkelsen, J.D. and Knox, J.P. 1999. Cell wall antibodies without immunisation: generation of and use of de-esterified homogalacturonan block-specific antibodies from a naïve phage display library. Plant J. 18: 57–65.Google Scholar
  50. Willats, W.G.T., Rasmussen, S.E., Kristensen, T., Mikkelsen, J.D. and Knox, J.P. 2002a. Sugar-coated microarrays: a novel slide surface for the high throughput analysis of glycans. Proteomics 2(12): in press.Google Scholar
  51. Willats, W.G.T., Steele-King, C.G. and Knox, J.P. 2002b. Antibody techniques. In: P. Gilmartin and C. Bowler (eds.), Molecular Plant Biology: a practical approach, Oxford University Press, Oxford, U.K.Google Scholar
  52. Willats, W.G.T., Steele-King, C.G., McCartney, L., Orfila, C., Marcus, S.E. and Knox, J.P. 2000. Making and using antibody probes to study plant cell walls. Plant Physiol. Biochem. 38(1-2): 27–36.Google Scholar
  53. Williams, M.N., Freshour, G., Darvill, A.G., Albersheim, P. and Hahn, M.G. 1996. An antibody Fab selected from a recombinant phage display library detects deesterified pectic polysaccharide rhamnogalacturonan II in plant cells. Plant Cell 8: 673–685.Google Scholar
  54. Wilson, D.S. and Nock, S. 2001. Functional protein microarrays. Curr. Opin. Chem. Biol. 6: 81–85.Google Scholar
  55. Winter, G. 1998a. Synthetic human antibodies and a strategy for protein engineering. FEBS Lett. 430: 92–94.Google Scholar
  56. Winter, G. 1998b. Making antibody and peptide ligands by repertoire selection technologies. J. Mol. Recogn. 11: 126–127.Google Scholar
  57. Winter, G., Griffiths, A.D., Hawkins, R.E. and Hoogenboom, H.R. 1994. Making antibodies by phage display technology. Annu. Rev. Immunol. 12: 433–455.Google Scholar
  58. Uetz, P. 2001. Two-hybrid arrays. Curr. Opin. Chem. Biol. 6: 57–62.Google Scholar
  59. Zucconi, A., Dente, L., Santonico, E., Castagnoli, L. and Cesareni, G. 2001. Selection of lgands by panning of domain libraries displayed on phage lambda reveals new potential partners of synaptojanin 1. J. Mol. Biol. 307: 1329–1339.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • William G.T. Willats
    • 1
    • 2
  1. 1.Department of Biochemistry and Molecular BiologyUK
  2. 2.University of LeedsWoodhouse Lane

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