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Progress in phage display: evolution of the technique and its applications

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Abstract

Phage display, the presentation of (poly)peptides as fusions to capsid proteins on the surface of bacterial viruses, celebrates its 25th birthday in 2010. The technique, coupled with in vitro selection, enables rapid identification and optimization of proteins based on their structural or functional properties. In the last two decades, it has advanced tremendously and has become widely accepted by the scientific community. This by no means exhaustive review aims to inform the reader of the key modifications in phage display. Novel display formats, innovative library designs and screening strategies are discussed. I will also briefly review some recent uses of the technology to illustrate its incredible versatility.

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References

  1. Pennazio S (2006) The origin of phage virology. Riv Biol 99:103–129

    PubMed  Google Scholar 

  2. Sulakvelidze A, Alavidze Z, Morris JG Jr (2001) Bacteriophage therapy. Antimicrob Agents Chemother 45:649–659

    Article  PubMed  CAS  Google Scholar 

  3. Maniatis T, Hardison RC, Lacy E, Lauer J, O’Connell C, Quon D, Sim GK, Efstratiadis A (1978) The isolation of structural genes from libraries of eucaryotic DNA. Cell 15:687–701

    Article  PubMed  CAS  Google Scholar 

  4. Sargent TD, Wu JR, Sala-Trepat JM, Wallace RB, Reyes AA, Bonner J (1979) The rat serum albumin gene: analysis of cloned sequences. Proc Natl Acad Sci USA 76:3256–3260

    Article  PubMed  CAS  Google Scholar 

  5. Zacher AN 3rd, Stock CA, Golden JW 2nd, Smith GP (1980) A new filamentous phage cloning vector: fd-tet. Gene 9:127–140

    Article  PubMed  CAS  Google Scholar 

  6. Hines JC, Ray DS (1980) Construction and characterization of new coliphage M13 cloning vectors. Gene 11:207–218

    Article  PubMed  CAS  Google Scholar 

  7. Kay BK, Winter J, McCafferty J (eds) (1996) Phage display of peptides and proteins. A laboratory manual. Academic, San Diego

    Google Scholar 

  8. Barbas CFI, Burton DR, Scott JK, Silverman GJ (eds) (2001) Phage display. A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York

  9. Clackson T, Lowman HB (eds) (2004) Phage display. A practical approach. Oxford University Press, New York

    Google Scholar 

  10. Sidhu SS (ed) (2005) Phage display in biotechnology and drug discovery. CRC, Boca Raton

  11. Aitken R (ed) (2009) Antibody Phage Display. Methods and Protocols. Humana, New York

    Google Scholar 

  12. Yan X, Xu Z (2006) Ribosome-display technology: applications for directed evolution of functional proteins. Drug Discov Today 11:911–916

    Article  PubMed  CAS  Google Scholar 

  13. Lipovsek D, Pluckthun A (2004) In vitro protein evolution by ribosome display and mRNA display. J Immunol Methods 290:51–67

    Article  PubMed  CAS  Google Scholar 

  14. Daugherty PS (2007) Protein engineering with bacterial display. Curr Opin Struct Biol 17:474–480

    Article  PubMed  CAS  Google Scholar 

  15. Pepper LR, Cho YK, Boder ET, Shusta EV (2008) A decade of yeast surface display technology: where are we now? Comb Chem High Throughput Screen 11:127–134

    Article  PubMed  CAS  Google Scholar 

  16. Ho M, Pastan I (2009) Mammalian cell display for antibody engineering. Methods Mol Biol 525:337–352 xiv

    PubMed  CAS  Google Scholar 

  17. Makela AR, Oker-Blom C (2008) The baculovirus display technology–an evolving instrument for molecular screening and drug delivery. Comb Chem High Throughput Screen 11:86–98

    Article  PubMed  CAS  Google Scholar 

  18. Michelfelder S, Lee MK, de Lima-Hahn E, Wilmes T, Kaul F, Muller O, Kleinschmidt JA, Trepel M (2007) Vectors selected from adeno-associated viral display peptide libraries for leukemia cell-targeted cytotoxic gene therapy. Exp Hematol 35:1766–1776

    Article  PubMed  CAS  Google Scholar 

  19. Smith GP (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 228:1315–1317

    Article  PubMed  CAS  Google Scholar 

  20. Bass S, Greene R, Wells JA (1990) Hormone phage: an enrichment method for variant proteins with altered binding properties. Proteins 8:309–314

    Article  PubMed  CAS  Google Scholar 

  21. Russel M, Lowman HB, Clackson T (2004) Introduction to phage biology and phage display. In: Clackson T, Lowman HB (eds) Phage display. A practical approach, vol 266. Oxford University Press, New York, pp 1–26

    Google Scholar 

  22. Smith GP (1993) Preface. Surface display and peptide libraries. Gene 128:1–2

    Article  Google Scholar 

  23. Smith GP, Petrenko VA (1997) Phage display. Chem Rev 97:391–410

    Article  PubMed  CAS  Google Scholar 

  24. Nanduri V, Sorokulova IB, Samoylov AM, Simonian AL, Petrenko VA, Vodyanoy V (2007) Phage as a molecular recognition element in biosensors immobilized by physical adsorption. Biosens Bioelectron 22:986–992

    Article  PubMed  CAS  Google Scholar 

  25. Crameri R, Suter M (1993) Display of biologically active proteins on the surface of filamentous phages: a cDNA cloning system for selection of functional gene products linked to the genetic information responsible for their production. Gene 137:69–75

    Article  PubMed  CAS  Google Scholar 

  26. Crameri R, Jaussi R, Menz G, Blaser K (1994) Display of expression products of cDNA libraries on phage surfaces. A versatile screening system for selective isolation of genes by specific gene-product/ligand interaction. Eur J Biochem 226:53–58

    Article  PubMed  CAS  Google Scholar 

  27. Faix PH, Burg MA, Gonzales M, Ravey EP, Baird A, Larocca D (2004) Phage display of cDNA libraries: enrichment of cDNA expression using open reading frame selection. Biotechniques 36:1018–1029

    PubMed  CAS  Google Scholar 

  28. Jespers LS, Messens JH, De Keyser A, Eeckhout D, Van den Brande I, Gansemans YG, Lauwereys MJ, Vlasuk GP, Stanssens PE (1995) Surface expression and ligand-based selection of cDNAs fused to filamentous phage gene VI. Biotechnology (N Y) 13:378–382

    Article  CAS  Google Scholar 

  29. Fuh G, Sidhu SS (2000) Efficient phage display of polypeptides fused to the carboxy-terminus of the M13 gene-3 minor coat protein. FEBS Lett 480:231–234

    Article  PubMed  CAS  Google Scholar 

  30. Fuh G, Pisabarro MT, Li Y, Quan C, Lasky LA, Sidhu SS (2000) Analysis of PDZ domain-ligand interactions using carboxyl-terminal phage display. J Biol Chem 275:21486–21491

    PubMed  CAS  Google Scholar 

  31. Gramatikoff K, Georgiev O, Schaffner W (1994) Direct interaction rescue, a novel filamentous phage technique to study protein-protein interactions. Nucleic Acids Res 22:5761–5762

    Article  PubMed  CAS  Google Scholar 

  32. Krebber C, Spada S, Desplancq D, Pluckthun A (1995) Co-selection of cognate antibody-antigen pairs by selectively-infective phages. FEBS Lett 377:227–231

    Article  PubMed  CAS  Google Scholar 

  33. Fields S, Song O (1989) A novel genetic system to detect protein-protein interactions. Nature 340:245–246

    Article  PubMed  CAS  Google Scholar 

  34. Legrain P, Selig L (2000) Genome-wide protein interaction maps using two-hybrid systems. FEBS Lett 480:32–36

    Article  PubMed  CAS  Google Scholar 

  35. Miller J, Stagljar I (2004) Using the yeast two-hybrid system to identify interacting proteins. Methods Mol Biol 261:247–262

    PubMed  CAS  Google Scholar 

  36. Gao C, Mao S, Lo CH, Wirsching P, Lerner RA, Janda KD (1999) Making artificial antibodies: a format for phage display of combinatorial heterodimeric arrays. Proc Natl Acad Sci USA 96:6025–6030

    Article  PubMed  CAS  Google Scholar 

  37. Gao C, Mao S, Kaufmann G, Wirsching P, Lerner RA, Janda KD (2002) A method for the generation of combinatorial antibody libraries using pIX phage display. Proc Natl Acad Sci USA 99:12612–12616

    Article  PubMed  CAS  Google Scholar 

  38. Kwasnikowski P, Kristensen P, Markiewicz WT (2005) Multivalent display system on filamentous bacteriophage pVII minor coat protein. J Immunol Methods 307:135–143

    Article  PubMed  CAS  Google Scholar 

  39. Weiss GA, Wells JA, Sidhu SS (2000) Mutational analysis of the major coat protein of M13 identifies residues that control protein display. Protein Sci 9:647–654

    PubMed  CAS  Google Scholar 

  40. Weiss GA, Sidhu SS (2000) Design and evolution of artificial M13 coat proteins. J Mol Biol 300:213–219

    Article  PubMed  CAS  Google Scholar 

  41. Sidhu SS (2001) Engineering M13 for phage display. Biomol Eng 18:57–63

    Article  PubMed  CAS  Google Scholar 

  42. Roth TA, Weiss GA, Eigenbrot C, Sidhu SS (2002) A minimized M13 coat protein defines the requirements for assembly into the bacteriophage particle. J Mol Biol 322:357–367

    Article  PubMed  CAS  Google Scholar 

  43. Held HA, Sidhu SS (2004) Comprehensive mutational analysis of the M13 major coat protein: improved scaffolds for C-terminal phage display. J Mol Biol 340:587–597

    Article  PubMed  CAS  Google Scholar 

  44. Sidhu SS, Feld BK, Weiss GA (2007) M13 bacteriophage coat proteins engineered for improved phage display. Methods Mol Biol 352:205–219

    PubMed  CAS  Google Scholar 

  45. Krumpe LR, Atkinson AJ, Smythers GW, Kandel A, Schumacher KM, McMahon JB, Makowski L, Mori T (2006) T7 lytic phage-displayed peptide libraries exhibit less sequence bias than M13 filamentous phage-displayed peptide libraries. Proteomics 6:4210–4222

    Article  PubMed  CAS  Google Scholar 

  46. Rosenberg A, Griffin K, Studier FW, McCormick M, Berg J, Novy R, Mierendorf R (1996) T7Select phage display system: a powerful new protein display system based on bacteriophage T7. Innovations 6:1–6

    Google Scholar 

  47. Iwasaki K, Trus BL, Wingfield PT, Cheng N, Campusano G, Rao VB, Steven AC (2000) Molecular architecture of bacteriophage T4 capsid: vertex structure and bimodal binding of the stabilizing accessory protein. Soc Virol 271:321–333

    Article  CAS  Google Scholar 

  48. Ren ZJ, Lewis GK, Wingfield PT, Locke EG, Steven AC, Black LW (1996) Phage display of intact domains at high copy number: a system based on SOC, the small outer capsid protein of bacteriophage T4. Protein Sci 5:1833–1843

    Article  PubMed  CAS  Google Scholar 

  49. Ren Z, Black LW (1998) Phage T4 SOC and HOC display of biologically active, full-length proteins on the viral capsid. Gene 215:439–444

    Article  PubMed  CAS  Google Scholar 

  50. Ren ZJ, Baumann RG, Black LW (1997) Cloning of linear DNAs in vivo by overexpressed T4 DNA ligase: construction of a T4 phage hoc gene display vector. Gene 195:303–311

    Article  PubMed  CAS  Google Scholar 

  51. Shivachandra SB, Li Q, Peachman KK, Matyas GR, Leppla SH, Alving CR, Rao M, Rao VB (2007) Multicomponent anthrax toxin display and delivery using bacteriophage T4. Vaccine 25:1225–1235

    Article  PubMed  CAS  Google Scholar 

  52. Li Q, Shivachandra SB, Leppla SH, Rao VB (2006) Bacteriophage T4 capsid: a unique platform for efficient surface assembly of macromolecular complexes. J Mol Biol 363:577–588

    Article  PubMed  CAS  Google Scholar 

  53. Efimov VP, Nepluev IV, Mesyanzhinov VV (1995) Bacteriophage T4 as a surface display vector. Virus Genes 10:173–177

    Article  PubMed  CAS  Google Scholar 

  54. Hoess RH (2002) Bacteriophage lambda as a vehicle for peptide and protein display. Curr Pharm Biotechnol 3:23–28

    Article  PubMed  CAS  Google Scholar 

  55. Sternberg N, Hoess RH (1995) Display of peptides and proteins on the surface of bacteriophage lambda. Proc Natl Acad Sci USA 92:1609–1613

    Article  PubMed  CAS  Google Scholar 

  56. Mikawa YG, Maruyama IN, Brenner S (1996) Surface display of proteins on bacteriophage lambda heads. J Mol Biol 262:21–30

    Article  PubMed  CAS  Google Scholar 

  57. Maruyama IN, Maruyama HI, Brenner S (1994) Lambda foo: a lambda phage vector for the expression of foreign proteins. Proc Natl Acad Sci USA 91:8273–8277

    Article  PubMed  CAS  Google Scholar 

  58. Dunn IS (1996) Total modification of the bacteriophage lambda tail tube major subunit protein with foreign peptides. Gene 183:15–21

    Article  PubMed  CAS  Google Scholar 

  59. Marks JD, Hoogenboom HR, Bonnert TP, McCafferty J, Griffiths AD, Winter G (1991) By-passing immunization. Human antibodies from V-gene libraries displayed on phage. J Mol Biol 222:581–597

    Article  PubMed  CAS  Google Scholar 

  60. Barbas CF 3rd, Kang AS, Lerner RA, Benkovic SJ (1991) Assembly of combinatorial antibody libraries on phage surfaces: the gene III site. Proc Natl Acad Sci USA 88:7978–7982

    Article  PubMed  CAS  Google Scholar 

  61. Hoogenboom HR, Griffiths AD, Johnson KS, Chiswell DJ, Hudson P, Winter G (1991) Multi-subunit proteins on the surface of filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains. Nucleic Acids Res 19:4133–4137

    Article  PubMed  CAS  Google Scholar 

  62. Waterhouse P, Griffiths AD, Johnson KS, Winter G (1993) Combinatorial infection and in vivo recombination: a strategy for making large phage antibody repertoires. Nucleic Acids Res 21:2265–2266

    Article  PubMed  CAS  Google Scholar 

  63. Sternberg N, Hamilton D (1981) Bacteriophage P1 site-specific recombination. I. Recombination between loxP sites. J Mol Biol 150:467–486

    Article  PubMed  CAS  Google Scholar 

  64. Tsurushita N, Fu H, Warren C (1996) Phage display vectors for in vivo recombination of immunoglobulin heavy and light chain genes to make large combinatorial libraries. Gene 172:59–63

    Article  PubMed  CAS  Google Scholar 

  65. Griffiths AD, Williams SC, Hartley O, Tomlinson IM, Waterhouse P, Crosby WL, Kontermann RE, Jones PT, Low NM, Allison TJ, Prospero TD, Hoogenboom HR, Nissim A, Cox JPL, Harrison JL, Zaccolo M, Gherardi E, Winter G (1994) Isolation of high affinity human antibodies directly from large synthetic repertoires. EMBO J 13:3245–3260

    PubMed  CAS  Google Scholar 

  66. Zahra DG, Vancov T, Dunn JM, Hawkins NJ, Ward RL (1999) Selectable in vivo recombination to increase antibody library size—an improved phage display vector system. Gene 227:49–54

    Article  PubMed  CAS  Google Scholar 

  67. Geoffroy F, Sodoyer R, Aujame L (1994) A new phage display system to construct multicombinatorial libraries of very large antibody repertoires. Gene 151:109–113

    Article  PubMed  CAS  Google Scholar 

  68. Sblattero D, Bradbury A (2000) Exploiting recombination in single bacteria to make large phage antibody libraries. Nat Biotechnol 18:75–80

    Article  PubMed  CAS  Google Scholar 

  69. Cen X, Bi Q, Zhu S (2006) Construction of a large phage display antibody library by in vitro package and in vivo recombination. Appl Microbiol Biotechnol 71:767–772

    Article  PubMed  CAS  Google Scholar 

  70. Collins J, Rottgen P (1997) Generation of diversity in combinatorial libraries. EP 9710539.1 (WO 98/33901)

  71. Collins J, Horn N, Wadenback J, Szardenings M (2001) Cosmix-plexing: a novel recombinatorial approach for evolutionary selection from combinatorial libraries. J Biotechnol 74:317–338

    PubMed  CAS  Google Scholar 

  72. Fisch I, Kontermann RE, Finnern R, Hartley O, Soler-Gonzalez AS, Griffiths AD, Winter G (1996) A strategy of exon shuffling for making large peptide repertoires displayed on filamentous bacteriophage. Proc Natl Acad Sci USA 93:7761–7766

    Article  PubMed  CAS  Google Scholar 

  73. Chasteen L, Ayriss J, Pavlik P, Bradbury AR (2006) Eliminating helper phage from phage display. Nucleic Acids Res 34:e145

    Article  PubMed  CAS  Google Scholar 

  74. Krebber A, Burmester J, Pluckthun A (1996) Inclusion of an upstream transcriptional terminator in phage display vectors abolishes background expression of toxic fusions with coat protein g3p. Gene 178:71–74

    Article  PubMed  CAS  Google Scholar 

  75. Beekwilder J, Rakonjac J, Jongsma M, Bosch D (1999) A phagemid vector using the E. coli phage shock promoter facilitates phage display of toxic proteins. Gene 228:23–31

    Article  PubMed  CAS  Google Scholar 

  76. Jestin JL, Volioti G, Winter G (2001) Improving the display of proteins on filamentous phage. Res Microbiol 152:187–191

    Article  PubMed  CAS  Google Scholar 

  77. Kristensen P, Winter G (1998) Proteolytic selection for protein folding using filamentous bacteriophages. Fold Des 3:321–328

    Article  PubMed  CAS  Google Scholar 

  78. Rondot S, Koch J, Breitling F, Dubel S (2001) A helper phage to improve single-chain antibody presentation in phage display. Nat Biotechnol 19:75–78

    Article  PubMed  CAS  Google Scholar 

  79. Kramer RA, Cox F, van der Horst M, van der Oudenrijn S, Res PC, Bia J, Logtenberg T, de Kruif J (2003) A novel helper phage that improves phage display selection efficiency by preventing the amplification of phages without recombinant protein. Nucleic Acids Res 31:e59

    Article  PubMed  CAS  Google Scholar 

  80. Baek H, Suk KH, Kim YH, Cha S (2002) An improved helper phage system for efficient isolation of specific antibody molecules in phage display. Nucleic Acids Res 30:e18

    Article  PubMed  Google Scholar 

  81. Soltes G, Barker H, Marmai K, Pun E, Yuen A, Wiersma EJ (2003) A new helper phage and phagemid vector system improves viral display of antibody Fab fragments and avoids propagation of insert-less virions. J Immunol Methods 274:233–244

    Article  PubMed  CAS  Google Scholar 

  82. Soltes G, Hust M, Ng KK, Bansal A, Field J, Stewart DI, Dubel S, Cha S, Wiersma EJ (2007) On the influence of vector design on antibody phage display. J Biotechnol 127:626–637

    Article  PubMed  CAS  Google Scholar 

  83. Olszewski A, Sato K, Aron ZD, Cohen F, Harris A, McDougall BR, Robinson WE Jr, Overman LE, Weiss GA (2004) Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lck. Proc Natl Acad Sci USA 101:14079–14084

    Article  PubMed  CAS  Google Scholar 

  84. Majumdar S, Hajduczki A, Mendez AS, Weiss GA (2008) Phage display of functional, full-length human and viral membrane proteins. Bioorg Med Chem Lett 18:5937–5940

    Article  PubMed  CAS  Google Scholar 

  85. van Houten NE, Zwick MB, Menendez A, Scott JK (2006) Filamentous phage as an immunogenic carrier to elicit focused antibody responses against a synthetic peptide. Vaccine 24:4188–4200

    Article  PubMed  CAS  Google Scholar 

  86. Zanghi CN, Lankes HA, Bradel-Tretheway B, Wegman J, Dewhurst S (2005) A simple method for displaying recalcitrant proteins on the surface of bacteriophage lambda. Nucleic Acids Res 33:e160

    Article  PubMed  Google Scholar 

  87. Tian F, Tsao ML, Schultz PG (2004) A phage display system with unnatural amino acids. J Am Chem Soc 126:15962–15963

    Article  PubMed  CAS  Google Scholar 

  88. Sandman KE, Benner JS, Noren CJ (2000) Phage display of selenopeptides. J Am Chem Soc 122:960–961

    Article  CAS  Google Scholar 

  89. Meyer SC, Shomin CD, Gaj T, Ghosh I (2007) Tethering small molecules to a phage display library: discovery of a selective bivalent inhibitor of protein kinase A. J Am Chem Soc 129:13812–13813

    Article  PubMed  CAS  Google Scholar 

  90. Woiwode TF, Haggerty JE, Katz R, Gallop MA, Barrett RW, Dower WJ, Cwirla SE (2003) Synthetic compound libraries displayed on the surface of encoded bacteriophage. Chem Biol 10:847–858

    Article  PubMed  CAS  Google Scholar 

  91. Dwyer MA, Lu W, Dwyer JJ, Kossiakoff AA (2000) Biosynthetic phage display: a novel protein engineering tool combining chemical and genetic diversity. Chem Biol 7:263–274

    Article  PubMed  CAS  Google Scholar 

  92. El Zoeiby A, Sanschagrin F, Darveau A, Brisson JR, Levesque RC (2003) Identification of novel inhibitors of Pseudomonas aeruginosa MurC enzyme derived from phage-displayed peptide libraries. J Antimicrob Chemother 51:531–543

    Article  PubMed  Google Scholar 

  93. D’Mello F, Howard CR (2001) An improved selection procedure for the screening of phage display peptide libraries. J Immunol Methods 247:191–203

    Article  PubMed  Google Scholar 

  94. Lunder M, Bratkovic T, Kreft S, Strukelj B (2005) Peptide inhibitor of pancreatic lipase selected by phage display using different elution strategies. J Lipid Res 46:1512–1516

    Article  PubMed  CAS  Google Scholar 

  95. Yu H, Dong X, Sun Y (2004) An alternating elution strategy for screening high affinity peptides from a phage display library. Biochem Eng J 18:169–175

    Article  CAS  Google Scholar 

  96. Zhuang G, Katakura Y, Furuta T, Omasa T, Kishimoto M, Suga K (2001) A kinetic model for a biopanning process considering antigen desorption and effective antigen concentration on a solid phase. J Biosci Bioeng 91:474–481

    Article  PubMed  CAS  Google Scholar 

  97. Kretzschmar T, Zimmermann C, Geiser M (1995) Selection procedures for nonmatured phage antibodies: a quantitative comparison and optimization strategies. Anal Biochem 224:413–419

    Article  PubMed  CAS  Google Scholar 

  98. Lunder M, Bratkovic T, Urleb U, Kreft S, Strukelj B (2008) Ultrasound in phage display: a new approach to nonspecific elution. Biotechniques 44:893–900

    Article  PubMed  CAS  Google Scholar 

  99. Malmborg AC, Duenas M, Ohlin M, Soderlind E, Borrebaeck CA (1996) Selection of binders from phage displayed antibody libraries using the BIAcore biosensor. J Immunol Methods 198:51–57

    Article  PubMed  CAS  Google Scholar 

  100. Yuan B, Schulz P, Sierks M-R (2006) Improved affinity selection using phage display technology and off-rate based selection. Electron J Biotechnol 9:171–175

    Google Scholar 

  101. Matsubara T, Ishikawa D, Taki T, Okahata Y, Sato T (1999) Selection of ganglioside GM1-binding peptides by using a phage library. FEBS Lett 456:253–256

    Article  PubMed  CAS  Google Scholar 

  102. Takakusagi Y, Takakusagi K, Kuramochi K, Kobayashi S, Sugawara F, Sakaguchi K (2007) Identification of C10 biotinylated camptothecin (CPT-10-B) binding peptides using T7 phage display screen on a QCM device. Bioorg Med Chem 15:7590–7598

    Article  PubMed  CAS  Google Scholar 

  103. Vanhercke T, Ampe C, Tirry L, Denolf P (2005) Rescue and in situ selection and evaluation (RISE): a method for high-throughput panning of phage display libraries. J Biomol Screen 10:108–117

    Article  PubMed  CAS  Google Scholar 

  104. Hogan S, Rookey K, Ladner R (2005) URSA: ultra rapid selection of antibodies from an antibody phage display library. Biotechniques 38:536–538

    Article  PubMed  CAS  Google Scholar 

  105. Morohashi K, Arai T, Saito S, Watanabe M, Sakaguchi K, Sugawara F (2006) A high-throughput phage display screening method using a combination of real-time PCR and affinity chromatography. Comb Chem High Throughput Screen 9:55–61

    Article  PubMed  CAS  Google Scholar 

  106. Plieva FM, Galaev IY, Noppe W, Mattiasson B (2008) Cryogel applications in microbiology. Trends Microbiol 16:543–551

    Article  PubMed  CAS  Google Scholar 

  107. Noppe W, Plieva F, Galaev IY, Pottel H, Deckmyn H, Mattiasson B (2009) Chromato-panning: an efficient new mode of identifying suitable ligands from phage display libraries. BMC Biotechnol 9:21

    Article  PubMed  CAS  Google Scholar 

  108. Castillo J, Goodson B, Winter J (2001) T7 displayed peptides as targets for selecting peptide specific scFvs from M13 scFv display libraries. J Immunol Methods 257:117–122

    Article  PubMed  CAS  Google Scholar 

  109. Wang WF, Cheng X, Molineux IJ (1999) Isolation and identification of fxsA, an Escherichia coli gene that can suppress F exclusion of bacteriophage T7. J Mol Biol 292:485–499

    Article  PubMed  CAS  Google Scholar 

  110. Bowley DR, Jones TM, Burton DR, Lerner RA (2009) Libraries against libraries for combinatorial selection of replicating antigen-antibody pairs. Proc Natl Acad Sci USA 106:1380–1385

    Article  PubMed  Google Scholar 

  111. Grøn H, Hyde-DeRuyscher R (2000) Peptides as tools in drug discovery. Curr Opin Drug Discov Dev 3:636–645

    Google Scholar 

  112. Schumacher TN, Mayr LM, Minor DL Jr, Milhollen MA, Burgess MW, Kim PS (1996) Identification of D-peptide ligands through mirror-image phage display. Science 271:1854–1857

    Article  PubMed  CAS  Google Scholar 

  113. Hawinkels LJ, van Rossenberg SM, de Jonge-Muller ES, Molenaar TJ, Appeldoorn CC, van Berkel TJ, Sier CF, Biessen EA (2007) Efficient degradation-aided selection of protease inhibitors by phage display. Biochem Biophys Res Commun 364:549–555

    Article  PubMed  CAS  Google Scholar 

  114. Rowley MJ, O’Connor K, Wijeyewickrema L (2004) Phage display for epitope determination: a paradigm for identifying receptor-ligand interactions. Biotechnol Annu Rev 10:151–188

    Article  PubMed  CAS  Google Scholar 

  115. Schooltink H, Rose-John S (2005) Designing cytokine variants by phage-display. Comb Chem High Throughput Screen 8:173–179

    Article  PubMed  CAS  Google Scholar 

  116. Hoogenboom HR (2002) Overview of antibody phage-display technology and its applications. Methods Mol Biol 178:1–37

    PubMed  CAS  Google Scholar 

  117. Conrad U, Scheller J (2005) Considerations on antibody-phage display methodology. Comb Chem High Throughput Screen 8:117–126

    Article  PubMed  CAS  Google Scholar 

  118. Skerra A (2007) Alternative non-antibody scaffolds for molecular recognition. Curr Opin Biotechnol 18:295–304

    Article  PubMed  CAS  Google Scholar 

  119. Gronwall C, Stahl S (2009) Engineered affinity proteins–generation and applications. J Biotechnol 140:254–269

    Article  PubMed  CAS  Google Scholar 

  120. Deperthes D (2002) Phage display substrate: a blind method for determining protease specificity. Biol Chem 383:1107–1112

    Article  PubMed  CAS  Google Scholar 

  121. Sedlacek R, Chen E (2005) Screening for protease substrate by polyvalent phage display. Comb Chem High Throughput Screen 8:197–203

    Article  PubMed  CAS  Google Scholar 

  122. Kay BK, Hamilton PT (2001) Identification of enzyme inhibitors from phage-displayed combinatorial peptide libraries. Comb Chem High Throughput Screen 4:535–543

    PubMed  CAS  Google Scholar 

  123. Sidhu SS, Koide S (2007) Phage display for engineering and analyzing protein interaction interfaces. Curr Opin Struct Biol 17:481–487

    Article  PubMed  CAS  Google Scholar 

  124. Hertveldt K, Belien T, Volckaert G (2009) General M13 phage display: M13 phage display in identification and characterization of protein-protein interactions. Methods Mol Biol 502:321–339

    Article  PubMed  CAS  Google Scholar 

  125. Fernandez-Gacio A, Uguen M, Fastrez J (2003) Phage display as a tool for the directed evolution of enzymes. Trends Biotechnol 21:408–414

    Article  PubMed  CAS  Google Scholar 

  126. Jung S, Honegger A, Pluckthun A (1999) Selection for improved protein stability by phage display. J Mol Biol 294:163–180

    Article  PubMed  CAS  Google Scholar 

  127. Sergeeva A, Kolonin MG, Molldrem JJ, Pasqualini R, Arap W (2006) Display technologies: application for the discovery of drug and gene delivery agents. Adv Drug Deliv Rev 58:1622–1654

    Article  PubMed  CAS  Google Scholar 

  128. Clonis YD (2006) Affinity chromatography matures as bioinformatic and combinatorial tools develop. J Chromatogr A 1101:1–24

    Article  PubMed  CAS  Google Scholar 

  129. Noppe W, Plieva FM, Vanhoorelbeke K, Deckmyn H, Tuncel M, Tuncel A, Galaev IY, Mattiasson B (2007) Macroporous monolithic gels, cryogels, with immobilized phages from phage-display library as a new platform for fast development of affinity adsorbent capable of target capture from crude feeds. J Biotechnol 131:293–299

    Article  PubMed  CAS  Google Scholar 

  130. Mao, C., Liu, A. and Cao, B. (2009) Virus-based chemical and biological sensing. Angew Chem Int Ed Engl 48:6790–6810

    Google Scholar 

  131. De Berardinis P, Haigwood NL (2004) New recombinant vaccines based on the use of prokaryotic antigen-display systems. Expert Rev Vaccines 3:673–679

    Article  PubMed  CAS  Google Scholar 

  132. Manoutcharian K, Gevorkian G, Cano A, Almagro JC (2001) Phage displayed biomolecules as preventive and therapeutic agents. Curr Pharm Biotechnol 2:217–223

    Article  PubMed  CAS  Google Scholar 

  133. Lee SC, Ibdah R, Van Valkenburgh C, Rowold E, Abegg A, Donnelly A, Klover J, Merlin S, McKearn JP (2001) Phage display mutagenesis of the chimeric dual cytokine receptor agonist myelopoietin. Leukemia 15:1277–1285

    Article  PubMed  CAS  Google Scholar 

  134. McConnell SJ, Dinh T, Le MH, Brown SJ, Becherer K, Blumeyer K, Kautzer C, Axelrod F, Spinella DG (1998) Isolation of erythropoietin receptor agonist peptides using evolved phage libraries. Biol Chem 379:1279–1286

    Article  PubMed  CAS  Google Scholar 

  135. Hyde-DeRuyscher R, Paige LA, Christensen DJ, Hyde-DeRuyscher N, Lim A, Fredericks ZL, Kranz J, Gallant P, Zhang J, Rocklage SM, Fowlkes DM, Wendler PA, Hamilton PT (2000) Detection of small-molecule enzyme inhibitors with peptides isolated from phage-displayed combinatorial peptide libraries. Chem Biol 7:17–25

    Article  PubMed  CAS  Google Scholar 

  136. Monoclonal antibody therapeutics 2009-2024. Market report. Visiongain. 06/08/2009

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

    Article  PubMed  CAS  Google Scholar 

  138. Bostrom J, Fuh G (2009) Design and construction of synthetic phage-displayed fab libraries. In: Aitken R (ed) Antibody phage display: methods and protocols, vol 562. Humana, New York, pp 17–35

    Chapter  Google Scholar 

  139. Lonberg N (2008) Human monoclonal antibodies from transgenic mice. Handb Exp Pharmacol 69–97

  140. Jespers LS, Roberts A, Mahler SM, Winter G, Hoogenboom HR (1994) Guiding the selection of human antibodies from phage display repertoires to a single epitope of an antigen. Biotechnology (N Y) 12:899–903

    Article  CAS  Google Scholar 

  141. Lonberg N (2008) Fully human antibodies from transgenic mouse and phage display platforms. Curr Opin Immunol 20:450–459

    Article  PubMed  CAS  Google Scholar 

  142. Williams A, Baird LG (2003) DX-88 and HAE: a developmental perspective. Transfus Apher Sci 29:255–258

    Article  PubMed  Google Scholar 

  143. Levy JH, O’Donnell PS (2006) The therapeutic potential of a kallikrein inhibitor for treating hereditary angioedema. Expert Opin Investig Drugs 15:1077–1090

    Article  PubMed  CAS  Google Scholar 

  144. Epstein TG, Bernstein JA (2008) Current and emerging management options for hereditary angioedema in the US. Drugs 68:2561–2573

    Article  PubMed  CAS  Google Scholar 

  145. Lehmann A (2008) Ecallantide (DX-88), a plasma kallikrein inhibitor for the treatment of hereditary angioedema and the prevention of blood loss in on-pump cardiothoracic surgery. Expert Opin Biol Ther 8:1187–1199

    Article  PubMed  CAS  Google Scholar 

  146. Nizak C, Monier S, del Nery E, Moutel S, Goud B, Perez F (2003) Recombinant antibodies to the small GTPase Rab6 as conformation sensors. Science 300:984–987

    Article  PubMed  CAS  Google Scholar 

  147. Gao J, Sidhu SS, Wells JA (2009) Two-state selection of conformation-specific antibodies. Proc Natl Acad Sci USA 106:3071–3076

    Article  PubMed  Google Scholar 

  148. Sakamoto K, Ito Y, Hatanaka T, Soni PB, Mori T, Sugimura K (2009) Discovery and characterization of a peptide motif that specifically recognizes a non-native conformation of human IgG induced by acidic pH conditions. J Biol Chem 284:9986–9993

    Article  PubMed  CAS  Google Scholar 

  149. Emadi S, Barkhordarian H, Wang MS, Schulz P, Sierks MR (2007) Isolation of a human single chain antibody fragment against oligomeric alpha-synuclein that inhibits aggregation and prevents alpha-synuclein-induced toxicity. J Mol Biol 368:1132–1144

    Article  PubMed  CAS  Google Scholar 

  150. Emadi S, Kasturirangan S, Wang MS, Schulz P, Sierks MR (2009) Detecting morphologically distinct oligomeric forms of alpha-synuclein. J Biol Chem 284:11048–11058

    Article  PubMed  CAS  Google Scholar 

  151. Segal DJ, Dreier B, Beerli RR, Barbas CF 3rd (1999) Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5′-GNN-3′ DNA target sequences. Proc Natl Acad Sci USA 96:2758–2763

    Article  PubMed  CAS  Google Scholar 

  152. Dreier B, Beerli RR, Segal DJ, Flippin JD, Barbas CF 3rd (2001) Development of zinc finger domains for recognition of the 5′-ANN-3′ family of DNA sequences and their use in the construction of artificial transcription factors. J Biol Chem 276:29466–29478

    Article  PubMed  CAS  Google Scholar 

  153. Dreier B, Fuller RP, Segal DJ, Lund CV, Blancafort P, Huber A, Koksch B, Barbas CF 3rd (2005) Development of zinc finger domains for recognition of the 5′-CNN-3′ family DNA sequences and their use in the construction of artificial transcription factors. J Biol Chem 280:35588–35597

    Article  PubMed  CAS  Google Scholar 

  154. Blancafort P, Magnenat L, Barbas CF 3rd (2003) Scanning the human genome with combinatorial transcription factor libraries. Nat Biotechnol 21:269–274

    Article  PubMed  CAS  Google Scholar 

  155. Kriplani U, Kay BK (2005) Selecting peptides for use in nanoscale materials using phage-displayed combinatorial peptide libraries. Curr Opin Biotechnol 16:470–475

    Article  PubMed  CAS  Google Scholar 

  156. Khoo X, Hamilton P, O’Toole GA, Snyder BD, Kenan DJ, Grinstaff MW (2009) Directed assembly of PEGylated-peptide coatings for infection-resistant titanium metal. J Am Chem Soc 131:10992–10997

    Article  PubMed  CAS  Google Scholar 

  157. Segvich SJ, Smith HC, Kohn DH (2009) The adsorption of preferential binding peptides to apatite-based materials. Biomaterials 30:1287–1298

    Article  PubMed  CAS  Google Scholar 

  158. Tomczak MM, Gupta MK, Drummy LF, Rozenzhak SM, Naik RR (2009) Morphological control and assembly of zinc oxide using a biotemplate. Acta Biomater 5:876–882

    Article  PubMed  CAS  Google Scholar 

  159. Nam KT, Wartena R, Yoo PJ, Liau FW, Lee YJ, Chiang YM, Hammond PT, Belcher AM (2008) Stamped microbattery electrodes based on self-assembled M13 viruses. Proc Natl Acad Sci USA 105:17227–17231

    Article  PubMed  Google Scholar 

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Acknowledgments

I am grateful to Miha Kosmač, Mojca Lunder and Matjaž Ravnikar for helpful discussions and critical reading of the manuscript. I apologize to those authors whose work is not mentioned due to space restrictions.

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Bratkovič, T. Progress in phage display: evolution of the technique and its applications. Cell. Mol. Life Sci. 67, 749–767 (2010). https://doi.org/10.1007/s00018-009-0192-2

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