Skip to main content
Log in

The applications of synthetic oligonucleotides to molecular biology

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Over the last few years, the chemical synthesis of DNA in vitro has become a routine technique. The ready availability of synthetic DNA has revolutionized molecular biological research and has enabled new research approaches to be attempted that had not been possible previously. The most commonly used approaches can be divided into three broad areas: the cloning and manipulation of genes, the diagnosis of diseases by probing gene structure, and the specific in vitro mutagenesis of DNA for structure/function studies. In this review, each of these three areas is discussed through specific applications from published work. This review is not intended to be comprehensive either in its scope or in its documentation of published results. Rather, it is meant to present some of the most commonly used applications of oligonucleotides in molecular biology through representative examples.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. H. G. Khorana. Science 203:614–625 (1979).

    Google Scholar 

  2. M. H. Caruthers. Science 230:281–285 (1985).

    Google Scholar 

  3. S. A. Narang. Tetrahedron 39:3–22 (1983).

    Google Scholar 

  4. J. E. Davies and H. G. Gassen. Angew. Chem. Int. Ed. Engl. 22:13–31 (1983).

    Google Scholar 

  5. K. Itakura, J. J. Rossi, and R. B. Wallace. Annu. Rev. Biochem. 53:323–356 (1984).

    Google Scholar 

  6. C. B. Reese. Tetrahedron 34:3143–3179 (1980).

    Google Scholar 

  7. E. Ohtsuka, M. Ikehara, and D. Soll. Nucleic Acids Res. 10:6553–6570 (1982).

    Google Scholar 

  8. R. C. Sheppard. Chem. Br. 19:402–429 (1983).

    Google Scholar 

  9. M. Gait. (ed.) Oligonucleotide Synthesis, IRL Press, Oxford, 1984.

    Google Scholar 

  10. T. Maniatis, R. C. Hardbon, E. Lacy, J. Laver, C. O'Connell, D. Quon, G. K. Sim, and A. Efstratiadis. Cell 15:687–701 (1970).

    Google Scholar 

  11. F. Rudgeon, P. Kovrilsky, and B. Mach. Nucleic Acids Res. 2:2365–2378 (1975).

    Google Scholar 

  12. T. Maniatis, S. G. Kee, A. Efstratiadis, and F. C. Kafatos. Cell 8:163–182 (1976).

    Google Scholar 

  13. S. Tonegawa, C. Brack, N. Hozumi, and R. Schuller. Proc. Natl. Acad. Sci. USA 74:3518–3522 (1977).

    Google Scholar 

  14. M. Oskarrson, W. L. McClements, D. O. Blair, J. V. Maizel, and G. F. van de Woude. Science 207:1222–1224 (1980).

    Google Scholar 

  15. D. DeFeo, M. A. Gonda, H. A. Young, E. H. Chang, D. R. Lowy, E. M. Scolnick, and R. W. Ellis. Proc. Natl. Acad. Sci. USA 78:3328–3332 (1981).

    Google Scholar 

  16. S. K. Niyogi and C. A. Thomas. J. Biol. Chem. 243:1220–1223 (1968).

    Google Scholar 

  17. P. Besmer, R. C. Miller, M. H. Caruthers, A. Kumar, K. Minamoto, J. H. van de Sande, N. Sidarova, and H. G. Khorana. J. Mol. Biol. 72:503–522 (1972).

    Google Scholar 

  18. R. Wu. Nature New Biol. 236:198–200 (1972).

    Google Scholar 

  19. R. Wu, C. P. D. Tu, and R. Padmanabhan. Biochem. Biophys. Res. Commun. 55:1092–1099 (1973).

    Google Scholar 

  20. M. T. Doel and M. Smith. FEBS Lett. 34:99–102 (1973).

    Google Scholar 

  21. W. Gilbert. Science 214:1305–1312 (1981).

    Google Scholar 

  22. F. Sanger. Science 214:1205–1210 (1981).

    Google Scholar 

  23. E. M. Southern. J. Mol. Biol. 98:503–517 (1975).

    Google Scholar 

  24. R. B. Wallace, J. Schaffer, R. F. Murphy, J. Bonner, T. Hirose, and K. Itakura. Nucleic Acids Res. 6:3543–3557 (1979).

    Google Scholar 

  25. J. B. Dodgson and R. D. Wells. Biochemistry 16:2367–2372 (1977).

    Google Scholar 

  26. J. W. Szostak, J. I. Stiles, B.-K. Tye, P. Chiu, F. Sherman, and R. C. Wu. Methods Enzymol. 68:419–428 (1979).

    Google Scholar 

  27. R. B. Wallace. In S. Woo (ed.), DNA Recombinant Technology: Methods, CRC Press, Cleveland, Ohio, 1984.

    Google Scholar 

  28. S. V. Suggs, T. Hirose, T. Miyake, E. H. Kawashima, M. J. Johnson, K. Itakura, and R. B. Wallace. In D. Brown (ed.), Developmental Biology Using Purified Genes, Academic Press, New York, 1982, pp. 683–693.

    Google Scholar 

  29. R. B. Wallace, M. J. Johnson, T. Hirose, T. Miyake, E. H. Kawashima, and K. Itakura. Nucleic Acids Res. 9:879–894 (1981).

    Google Scholar 

  30. Y. Ike, S. Ikuta, M. Sato, T. Huang, and K. Itakura. Nucleic Acids Res. 11:477–488 (1983).

    Google Scholar 

  31. S. V. Suggs, R. B. Wallace, T. Hirose, E. H. Kawashima, and K. Itakura. Proc. Natl. Acad. Sci. USA 78:6613–6617 (1981).

    Google Scholar 

  32. B. A. Cunningham, J. L. Wang, I. Berggard, and P. A. Peterson. Biochemistry 12:4811–4821 (1973).

    Google Scholar 

  33. A. S. Whitehead, G. Goldberger, D. E. Woods, A. F. Markham, and R. Colten. Proc. Natl. Acad. Sci. USA 80:5387–5391 (1983).

    Google Scholar 

  34. J. Singer-Sam, R. L. Simmer, D. H. Keith, L. Shively, M. Teplitz, K. Itakura, S. M. Gartler, and A. D. Riggs. Proc. Natl. Acad. Sci. USA 80:802–806 (1983).

    Google Scholar 

  35. J. B. Hurley, H. K. W. Fong, D. B. Teplow, W. J. Dreyer, and M. I. Simon. Proc. Natl. Acad. Sci. USA 81:6948–6952 (1984).

    Google Scholar 

  36. M. A. Bourdon, A. Oldberg, M. Pierschbacker, and E. Ruoslahti. Proc. Natl. Acad. Sci. USA 82:1321–1325 (1985).

    Google Scholar 

  37. W. I. Wood, D. J. Capon, C. C. Simonsen, D. C. Eaton, J. Gitschier, B. Keyt, P. H. Seeburg, D. H. Smith, P. Hollingshead, K. L. Wion, E. Delwart, E. G. D. Tuddenham, G. A. Vehar, and R. M. Lawn. Nature 312:330–337 (1984).

    Google Scholar 

  38. J. J. Toole, J. L. Knopf, J. M. Wozney, L. A. Sultzman, J. L. Buecker, D. D. Pittman, R. J. Kaufman, E. Brown, C. Shoemaker, E. C. Orr, G. W. Amphlett, W. B. Foster, M. L. Coe, G. J. Knutson, D. N. Fass, and R. M. Hewick. Nature 212:342–347 (1984).

    Google Scholar 

  39. M. Jaye, H. de la Salle, F. Schamber, A. Balland, V. Kohli, A. Findeli, P. Tolstoshev, and J.-P. Lecocq. Nucleic Acids Res. 11:2325–2335 (1983).

    Google Scholar 

  40. K. L. Agarwal, T. J. Brunsted, and B. E. Noyes. J. Biol. Chem. 256:1023–1028 (1981).

    Google Scholar 

  41. S. Anderson and I. B. Kingston. Proc. Natl. Acad. Sci. USA 80:6838–6842 (1983).

    Google Scholar 

  42. A. Ullrich, C. H. Berman, T. J. Dull, A. Gray, and J. M. Lee. EMBO J. 3:361–364 (1984).

    Google Scholar 

  43. B. S. Segundo, S. J. Chan, and D. F. Steiner. Proc. Natl. Acad. Sci. USA 82:2320–2324 (1985).

    Google Scholar 

  44. A. Ullrich, J. R. Bell, E. Y. Chen, R. Herrera, L. M. Petruzzelli, T. J. Dull, A. Gray, L. Coussens, Y.-C. Liao, M. Tsubokura, A. Mason, P. H. Seeburg, C. Grunfeld, O. M. Rosen, and J. Ramachandran. Nature 313:756–761 (1985).

    Google Scholar 

  45. R. Lathe. J. Mol. Biol. 183:1–12 (1985).

    Google Scholar 

  46. M. Noda, Y. Furutani, H. Takahashi, M. Toyosato, T. Hirose, S. Inayama, S. Nakanishi, and S. Numa. Nature 295:202–208 (1982).

    Google Scholar 

  47. A. Ullrich, A. Gray, C. Berman, and T. J. Dull. Nature 303:821–825 (1983).

    Google Scholar 

  48. D. Pennica, W. E. Holmes, W. J. Kohr, R. N. Harkins, G. A. Vehar, C. A. Ward, W. F. Bennett, E. Yelverton, P. H. Seeburg, H. L. Heyneker, and D. V. Goeddel. Nature 301:214–221 (1983).

    Google Scholar 

  49. D. Cosman, D. P. Cerretti, A. Larsen, L. Park, C. March, S. Dower, S. Gillis, and D. Urdal. Nature 312:768–771 (1984).

    Google Scholar 

  50. E. Ohtsuka, S. Matsuki, M. Ikehara, Y. Takahashi, and K. Matsubara. J. Biol. Chem. 260:2605–2608 (1985).

    Google Scholar 

  51. T. Huynh-Dinh, N. Duchange, M. M. Zakin, A. Lemarchand, and J. Igolen. Proc. Natl. Acad. Sci. USA 82:7510–7514 (1985).

    Google Scholar 

  52. G. E. Shull, A. Schwartz, and J. B. Lingrel Nature 316:691–695 (1985).

    Google Scholar 

  53. D. H. MacLennan, C. J. Brandl, B. Korczak, and N. M. Green. Nature 316:696–700 (1985).

    CAS  PubMed  Google Scholar 

  54. G. G. Wong, J. S. Witek, P. A. Temple, K. M. Wilkens, A. C. Leary, D. P. Luxenberg, S. S. Jones, E. L. Brown, R. M. Kay, E. C. Orr, C. Shoemaker, D. W. Golde, R. J. Kaufman, R. M. Hewick, E. A. Wang, and S. C. Clark. Science 228:810–815 (1985).

    Google Scholar 

  55. A. Bollen, A. Herzog, A. Cravador, P. Herion, P. Chuchana, A. van der Straten, R. Loriau, P. Jacobs, and A. van Elsen. DNA 2:255–264 (1983).

    Google Scholar 

  56. M. Courtney, A. Buchwalder, L.-H. Tessier, M. Jaye, A. Benavente, A. Balland, C. Kohli, R. Lathe, P. Tolstoshev, and J.-P. Lecocq. Proc. Natl. Acad. Sci. USA 81:669–673 (1984).

    Google Scholar 

  57. S. Rosenberg, P. J. Barr, R. C. Najarian, and R. A. Hallewell. Nature 312:77–80 (1984).

    Google Scholar 

  58. D. H. Calhoun, D. F. Bishop, H. S. Bernstein, M. Quinn, P. Hantzopoulos, and R. J. Desnick. Proc. Natl. Acad. Sci. USA 82:7364–7368 (1985).

    Google Scholar 

  59. T. J. Knott, S. C. Rall, Jr., T. L. Innerarity, S. F. Jacobson, M. S. Urdea, B. Levy-Wilson, L. M. Powell, R. J. Pease, R. Eddy, H. Nakai, M. Byers, L. M. Priestley, E. Robertson, L. B. Rall, C. Betsholtz, T. V. Shows, R. W. Mahley, and J. Scott. Science 230:37–43 (1985).

    Google Scholar 

  60. E. S. Kawasaki, M. B. Ladner, A. M. Wang, J. van Arsdell, M. K. Warren, M. Y. Coyne, V. L. Schweickart, M.-T. Lee, K. J. Wilson, A. Boosman, E. R. Stanley, P. Ralph, and D. F. Mark. Science 230:291–296 (1985).

    Google Scholar 

  61. K. Jacobs, C. Shoemaker, R. Rudersdorf, S. D. Neill, R. J. Kaufman, A. Mufson, J. Sechra, S. S. Jones, R. Hewick, E. F. Fritsch, M. Kawakita, T. Shimizu, and T. Miyake. Nature 313:806–810 (1985).

    Google Scholar 

  62. R. G. DiScipio, M. R. Gehring, E. R. Podack, C. C. Kan, T. E. Hugli, and G. H. Fey. Proc. Natl. Acad. Sci. USA 81:7298–7302 (1984).

    Google Scholar 

  63. E. V. Prochownik, A. F. Markham, and S. H. Orkin. J. Biol. Chem. 258:8389–8394 (1983).

    Google Scholar 

  64. P. Jacobs, A. Cravador, R. Loriau, F. Brockly, B. Colau, P. Chuchana, A. van Elsen, A. Herzog, and A. Bollen. DNA 4:139–146 (1985).

    Google Scholar 

  65. K. E. Mayo, W. Vale, J. Rivier, M. G. Rosenfeld, and R. M. Evans. Nature 306:86–88 (1983).

    Google Scholar 

  66. E. Ohtsuka, Y. Taniyama, S. Iwai, K. Kitano, S. Miyamoto, T. Ohgi, Y. Sakuragawa, K. Fujiyama, T. Ikari, M. Kobayashi, T. Miyake, S. Shibahara, T. Tokunaga, M. Ikehara, A. Ono, T. Veda, T. Tanaka, H. Baba, T. Miki, A. Sakurai, and T. Oishi. Nucleic Acid Res. Symp. Ser. 12:79–82 (1983).

    Google Scholar 

  67. M. S. Urdea, J. P. Merryweather, G. T. Mullenbach, D. Cort, U. Heberlen, P. Valenzuela, and P. J. Barr. Proc. Natl. Acad. Sci. USA 80:7461–7467 (1983).

    Google Scholar 

  68. B. S. Sproat and M. J. Gait. Nucleic Acids Res. 13:2959–2977 (1985).

    Google Scholar 

  69. W. Mandecki, K. W. Mollison, T. J. Bolling, B. S. Powell, G. W. Carter, and J. L. Fox. Proc. Natl. Acad. Sci. USA 82:3543–3547 (1985).

    Google Scholar 

  70. M. D. Edge, A. R. Greene, G. R. Heathcliffe, P. A. Meacock, W. Schuch, D. B. Scanlon, T. C. Atkinson, C. R. Newton, and A. F. Markham. Nature 292:756–760 (1981).

    Google Scholar 

  71. J. J. Rossi, R. Kierzek, T. Huang, P. Walker, and K. Itakura. J. Biol. Chem. 257:9226–9229 (1982).

    Google Scholar 

  72. R. C. Scarpulla, S. A. Narang, and R. Wu. Anal. Bio. Chem. 121:353–365 (1982).

    Google Scholar 

  73. M. Gouy and C. Gautier. Nucleic Acids Res. 10:7055–7074 (1982).

    Google Scholar 

  74. J. L. Bennetzen and B. D. Hall. J. Biol. Chem. 257:3026–3031 (1982).

    Google Scholar 

  75. G. A. Bitter and K. M. Egan. Gene 32:263–274 (1984).

    Google Scholar 

  76. J. D. Windass, C. R. Newton, J. DeMaeyer-Guignard, V. E. Moore, and A. F. Markham. Nucleic Acids Res. 10:6639–6658 (1982).

    Google Scholar 

  77. P. L. deHaseth, R. A. Goldman, C. L. Cech, and M. H. Caruthers. Nucleic Acids Res. 11:773–787 (1983).

    Google Scholar 

  78. T. Miyake, T. Oka, S. Sumi, and M. Susuki. Nucleic Acids Res. Symp. 11:81–83 (1982).

    Google Scholar 

  79. J. J. Rossi, X. Soberon, Y. Marumoto, J. McMahon, and K. Itakura. Proc. Natl. Acad. Sci. USA 80:3203–3207 (1983).

    Google Scholar 

  80. J. Messing, B. Gronenborn, B. Muller-Hill, and P. H. Hofschneider. Proc. Natl. Acad. Sci. USA 74:3642–3646 (1977).

    Google Scholar 

  81. J. Messing, R. Crea, and P. H. Seeburg. Nucleic Acids Res. 9:309–321 (1981).

    Google Scholar 

  82. P. P. Lau and H. B. Gray. Nucleic Acids Res. 6:331–339 (1979).

    Google Scholar 

  83. S. L. McKnight and R. Kingsbury. Science 217:316–324 (1982).

    Google Scholar 

  84. S. McKnight. Cell 31:355–365 (1982).

    Google Scholar 

  85. R. A. Flavell, J. M. Kooter, E. DeBoer, P. F. R. Little, and R. Williamson. Cell 15:25–41 (1978).

    Google Scholar 

  86. R. F. Geever, L. B. Wilson, F. S. Nallaseth, P. F. Milner, M. Bittner, and J. T. Wilson. Proc. Natl. Acad. Sci. USA 78:5081–5082 (1981).

    Google Scholar 

  87. J. C. Chang and Y. W. Kan. N. Engl. J. Med. 307:30–32 (1982).

    Google Scholar 

  88. S. H. Orkin, P. F. R. Little, H. H. Kazazian, and C. D. Boehm. N. Engl. J. Med. 307:32–36 (1982).

    Google Scholar 

  89. M. Goossens, K. Y. Lee, S. A. Liebhaber, and Y. W. Kan. Nature 296:864–865 (1982).

    Google Scholar 

  90. K. Kurachi, T. Chandra, S. J. F. Degen, T. T. White, T. L. Marchioro, S. L. C. Woo, and E. W. Davie. Proc. Natl. Acad. Sci. USA 78:6826–6830 (1981).

    Google Scholar 

  91. R. B. Wallace, M. Schold, M. J. Johnson, P. Dembeck, and K. Itakura. Nucleic Acids Res. 9:3647–3656 (1981).

    Google Scholar 

  92. B. J. Conner, A. A. Reyes, C. Morin, K. Itakura, R. L. Teplitz, and R. B. Wallace. Proc. Natl. Acad. Sci. USA 80:278–282 (1983).

    Google Scholar 

  93. L. Pauling, H. A. Itano, S. J. Singer, and I. C. Wells. Science 25:543–548 (1949).

    Google Scholar 

  94. T. M. Shinnick, E. Lund, O. Smithies, and F. R. Blattner. Nucleic Acids Res. 2:1911–1929 (1975).

    Google Scholar 

  95. S. H. Orkin, A. F. Markham, and H. H. Kazazian. J. Clin Invest. 71:775–779 (1983).

    Google Scholar 

  96. M. Piratsu, Y. W. Kan, A. Cao, B. J. Conner, R. L. Teplitz, and R. B. Wallace. N. Engl. J. Med. 309:284–287 (1983).

    Google Scholar 

  97. V. J. Kidd, R. B. Wallace, K. Itakura, and S. L. C. Woo. Nature 304:230–234 (1983).

    Google Scholar 

  98. N. M. Green. Adv. Protein Chem. 29:85–133 (1975).

    Google Scholar 

  99. J. E. Manning, N. D. Hershey, T. R. Broker, M. Pellegrini, and N. Davidson. Chromosoma 53:107–117 (1975).

    Google Scholar 

  100. P. R. Langer, A. A. Waldrop, and D. C. Ward. Proc. Natl. Acad. Sci. USA 78:6633–6637 (1981).

    Google Scholar 

  101. J. J. Leary, D. J. Brigati, and D. C. Ward. Proc. Natl. Acad. Sci. USA 80:4045–4049 (1983).

    Google Scholar 

  102. A. Murasugi and R. B. Wallace. DNA 3:269–277 (1984).

    Google Scholar 

  103. T. Kempe, W. I. Sundquist, F. Chow, and S.-L. Hu. Nucleic Acids Res. 13:45–57 (1985).

    Google Scholar 

  104. A. B. Studencki and R. B. Wallace. DNA 3:7–15 (1984).

    Google Scholar 

  105. D. Shortle, D. DiMaio, and D. Nathans. Annu. Rev. Genet. 15:265–294 (1981).

    Google Scholar 

  106. D. Botstein and D. Shortle. Science 229:1193–1201 (1985).

    Google Scholar 

  107. M. Smith. Annu. Rev. Genet. 19:423–462 (1985).

    Google Scholar 

  108. A. Razin, T. Hirose, K. Itakura, and A. D. Riggs. Proc. Natl. Acad. Sci. USA 75:4268–4270 (1978).

    Google Scholar 

  109. S. Gilliam and M. Smith. Gene 8:81–97 (1979).

    Google Scholar 

  110. S. Gilliam and M. Smith. Gene 8:99–106 (1979).

    Google Scholar 

  111. R. B. Wallace, P. F. Johnson, S. Tanaka, M. Schold, K. Itakura, and J. Abelson. Science 209:1396–1400 (1980).

    Google Scholar 

  112. M. Schold, A. Colombero, A. A. Reyes, and R. B. Wallace. DNA 3:469–477 (1984).

    Google Scholar 

  113. M. J. Zoller and M. Smith. Nucleic Acids Res. 10:6487–6500 (1982).

    Google Scholar 

  114. M. J. Zoller and M. Smith. Methods Enzymol. 100:469–500 (1983).

    Google Scholar 

  115. M. J. Zoller and M. Smith. DNA 3:479–488 (1984).

    Google Scholar 

  116. K. Norris, F. Norris, L. Christiansen, and N. Fiil. Nucleic Acids Res. 11:5103–5112 (1983).

    Google Scholar 

  117. C. E. Bauer, S. D. Hesse, D. A. Waechter-Brulla, S. P. Lynn, R. I. Gumport, and J. F. Gardner. Gene 37:73–81 (1985).

    Google Scholar 

  118. P. Carter, H. Bedouelle, and G. Winter. Nucleic Acids Res. 13:4431–4442 (1985).

    Google Scholar 

  119. G. K. Ackers and F. R. Smith. Annu. Rev. Biochem. 54:597–629 (1985).

    Google Scholar 

  120. G. Dalbadie-McFarland, L. W. Cohen, A. D. Riggs, C. Morin, K. Itakura, and J. H. Richards. Proc. Natl. Acad. Sci. USA 79:6409–6413 (1982).

    Google Scholar 

  121. I. S. Sigal, B. G. Harwood, and R. Arentzen. Proc. Natl. Acad. Sci. USA 79:7157–7160 (1982).

    Google Scholar 

  122. I. S. Sigal, W. F. DeGrado, B. J. Thomas, and S. R. Petteway. J. Biol. Chem. 259:5327–5332 (1984).

    Google Scholar 

  123. G. Winter, A. R. Fersht, A. J. Wilkinson, M. Zoller, and M. Smith. Nature 299:756–788 (1982).

    Google Scholar 

  124. A. J. Wilkinson, A. R. Fersht, D. M. Blow, P. Carter, and G. Winter. Nature 307:187–188 (1984).

    Google Scholar 

  125. J. E. Villafranca, E. E. Howell, D. H. Voet, M. S. Strobel, R. C. Ogden, J. N. Abelson, and J. Kraut. Science 222:782–788 (1983).

    Google Scholar 

  126. S. Gutteridge, I. Sigal, B. Thomas, R. Arentzen, A. Cordova, and G. Lorimer. EMBO J. 3:2737–2743 (1984).

    Google Scholar 

  127. J. Travis, M. Owen, P. George, R. Carrell, S. Rosenberg, R. A. Hallewell, and P. J. Barr. J. Biol. Chem. 260:4384–4369 (1985).

    Google Scholar 

  128. M. Courtney, S. Jallat, L.-H. Tessier, A. Benavente, R. G. Crystal, and J.-P. Lecocq. Nature 313:149–151 (1985).

    Google Scholar 

  129. G. J. Pielak, A. G. Mauk, and M. Smith. Nature 313:152–154 (1985).

    Google Scholar 

  130. M. Mishina, T. Tobimatsu, K. Imoto, K. Tanaka, Y. Fujita, K. Fukuda, M. Kurasaki, H. Takahashi, Y. Morimoto, T. Hirose, S. Inayama, T. Takahashi, M. Kuno, and S. Numa. Nature 313:364–369 (1985).

    Google Scholar 

  131. C. E. Stauffer and D. Etson. J. Biol. Chem. 244:5333–5338 (1969).

    Google Scholar 

  132. D. A. Estell, T. P. Graycar, and J. A. Wells. J. Biol. Chem. 260:6518–6521 (1985).

    Google Scholar 

  133. J. A. Wells, M. Vasser, and D. B. Powers. Gene 34:315–323 (1985).

    Google Scholar 

  134. P. G. Thomas, A. J. Russell, and A. R. Fersht. Nature 318:375–376 (1985).

    Google Scholar 

  135. C. S. Craik, C. Largman, T. Fletcher, S. Roczniak, P. J. Barr, R. Fletterick, and W. J. Rutter. Science 228:191–297 (1985).

    Google Scholar 

  136. S. J. Gardell, C. S. Craik, D. Hilvert, M. S. Urdea, and W. J. Rutter. Nature 317:551–555 (1985).

    Google Scholar 

  137. R. B. Wallace, P. F. Johnson, S. Tanaka, M. Schold, K. Itakura, and J. Abelson. Science 209:1396–1400 (1980).

    Google Scholar 

  138. T. Zarucki-Schulz, S. Y. Tsai, K. Itakura, X. Soberon, R. B. Wallace, M.-J. Tsai, S. L. C. Woo, and B. W. O'Malley. J. Biol. Chem. 257:11070–11077 (1982).

    Google Scholar 

  139. M. Kozak. Nature 308:241–246 (1984).

    Google Scholar 

  140. A. D. Charles, A. E. Gautier, M. D. Edge and J. R. Knowles. J. Biol. Chem. 14:7930–7932 (1982).

    Google Scholar 

  141. S. Inouye, X. Soberon, T. Franceschini, K. Nakamura, K. Irakura, and M. Inouye. Proc. Natl. Acad. Sci. USA 79:3438–3441 (1982).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ellis, R.W. The applications of synthetic oligonucleotides to molecular biology. Pharm Res 3, 195–207 (1986). https://doi.org/10.1023/A:1016382512330

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1016382512330

Navigation