EJB Reviews pp 165-179 | Cite as

Concepts and strategies for human gene therapy

  • Klaus Roemer
  • Theodore Friedmann
Part of the EJB Reviews book series (EJB REVIEWS, volume 1992)


Beginning in the late 1960s and early 1970s, the availability of new molecular-biological tools and concepts began to suggest that designed genetic changes may eventually provide a new and effective form for the therapy of human diseases. In 1972, the medical need, as well as the technical and conceptual issues involved in efficient virally mediated gene transfer for therapeutic purposes, were outlined (Friedmann and Roblin, 1972). In the 20 years since that time, progress has been so great that human experiments are now underway to test the efficacy of foreign genes in defective human cells as a form of gene therapy. There are a very large number of human diseases that represent potential targets for this kind of manipulation. More than 4500 human diseases are currently classified as genetic (McKusick, 1988). Until now, only a very small minority of these diseases has been associated with specific mutations in the human genome. Recessive genetic diseases like cystic fibrosis and adenosine deaminase (ADA) deficiency require mutations to be present in both alleles of a gene in order to generate the disease phenotype, while dominant diseases like Huntington’s disease can be caused by the presence of only one mutated copy of a gene. The mere presence of a mutant allele overrides the remaining normal allele and leads to disease. With the application of the tools of molecular genetics, and with new approaches to the identification and characterization of disease-related defects, therapy through the correction of genetic defects has come within reach (Friedmann, 1989; Anderson 1992). Most modern gene-therapeutic approaches are based on the introduction of functional copies of defective genes into cells.


Gene Therapy Long Terminal Repeat Adenosine Deaminase Latency Associate Transcript Internal Promoter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



human immunodeficiency virus


acquired immune-deficiency syndrome


adenosine deaminase


low-density lipoproteins


cystic-fibrosis transmembrane-conductance regulator


long terminal repeats


multidrug resistance


herpes simplex virus.


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  1. Acsadi, G., Dickson, G., Love, D. R., Jani, A., Walsh, F. S., Gurusinghe, A., Wolff, J. A. & Davies, K. E. (1991) Nature 352, 815–818.PubMedGoogle Scholar
  2. Adam, M. A., Ramesh, N., Miller, A. D. & Osborne, W. R. A. (1991) J. Virol. 65, 4985–4990.PubMedGoogle Scholar
  3. Anderson, W. F. (1992) Science 256, 808–813.PubMedGoogle Scholar
  4. Armentano, D., Thompson, A. R., Darlington, G. & Woo, S. L. C. (1990) Proc. Natl Acad. Sci. USA 87, 6141–6145.PubMedGoogle Scholar
  5. Baker, S. J., Markowitz, S., Fearon, E. R., Willson, J. K. & Vogelstein, B. (1990) Science 249, 912–915.PubMedGoogle Scholar
  6. Barr, E. & Leiden, J. M. (1991) Science 254, 1507–1509.PubMedGoogle Scholar
  7. Berkner, K. L. (1988) Biotechniques 6, 616–629.PubMedGoogle Scholar
  8. Bestwick, R. K., Kozak, S. L. & Kabat, D. (1988) Proc. Natl Acad. Sci. USA 85, 8504–8508.Google Scholar
  9. Bishop, J. M. (1991) Cell 64, 235–248.PubMedGoogle Scholar
  10. Bodine, D. M., McDonagh, K. T., Brandt, S. J., Ney, P. A., Agricola, B., Byrne, E. & Nienhuis, A. W. (1990) Proc. Natl Acad. Sci. USA 87, 3738–3742.PubMedGoogle Scholar
  11. Bodine, D. M., McDonagh, K. T., Seidel, N. E. & Nienhuis, A. W. (1991) Exp. Hematol. 19, 206–212.PubMedGoogle Scholar
  12. Breakefield, X. O. & DeLuca, N. A. (1991) New Biol. 3, 203–218.Google Scholar
  13. Buerstedde, J.-M. & Takeda, S. (1991) Cell 67, 179–188.PubMedGoogle Scholar
  14. Calabretta, B. (1991)Cancer Res. 51, 4505–4510.PubMedGoogle Scholar
  15. Capecchi, M.(1980)Cell 22, 479–488.PubMedGoogle Scholar
  16. Cheng, J., Yee, J.-K., Yeargin, J., Friedmann, T. & Haas, M. (1992) Cancer Res. 52, 222–226.PubMedGoogle Scholar
  17. Chiocca, E. A., Choi, B. B., Cai, W., DeLuca, N. A., Schaffer, P. A., DiFiglia, M., Breakefield, X. O. & Martuza, R. L. (1990)New Biol. 2, 139–146. Google Scholar
  18. Chowdhury, J. R., Grossman, M., Gupta, S., Chowdhury, N. R., Baker, J. R. Jr & Wilson, J. M. (1991) Science 254, 1802–1805.PubMedGoogle Scholar
  19. Collins, F. S. (1992) Science 256, 774–779.PubMedGoogle Scholar
  20. Corey, C. A., DeSilva, A., Holland, C. & Williams, D. A. (1990) Blood 75, 337–343.PubMedGoogle Scholar
  21. Cornetta, K., Morgan, R. A., Gillio, A., Sturm, S., Baltrucki, L., O’Reilly, R. & Anderson, W. F. (1991) Hum. Gene Ther. 2, 215–219.PubMedGoogle Scholar
  22. DeLuca, N. A., McCarthy, A. M. & Schaffer, P. A. (1985) J. Virol. 56, 558–570.PubMedGoogle Scholar
  23. Dhawan, J., Pan, L. C., Pavlath, G. K., Travis, M. A., Lanctot, A. M. & Blau, H. M. (1991) Science 254, 1509–1512.PubMedGoogle Scholar
  24. Dick, J. E., Magli, M. C., Huszar, D., Phillips, R. A. & Bernstein, A. (1985) Cell 42, 71–79.PubMedGoogle Scholar
  25. Dobson, A. T., Sederati, F., Devi-Rao, G., Flanagan, W. M., Farrell, M. J., Stevens, J. G, Wagner, E. K. & Feldman, L. T. (1989) J. Virol. 63, 3844–3851.PubMedGoogle Scholar
  26. Dobson, A. T., Margolis, T. P., Sedarati, F., Stevens, J. G. & Feldman, L. T. (1990) Neuron 5, 353–360.PubMedGoogle Scholar
  27. Dzierzak, E. A., Papayannopoulou, T. & Mulligan, R. C. (1988) Nature 331, 35–41.PubMedGoogle Scholar
  28. Eglitis, M. A. & Anderson, W. F. (1988) Biotechniques 6, 608–614.PubMedGoogle Scholar
  29. Eglitis, M. A. (1991) Hum. Gene Ther. 2, 195–201.PubMedGoogle Scholar
  30. Einerhand, M. P. W., Bakx, T. A. & Valerio, D. (1991) Hum. Gene Ther. 2, 301–306.PubMedGoogle Scholar
  31. Eisenberg, C., Seta, N., Appel, M., Feldmann, G., Durand, G. & Feger, J. (1991) J. Hepatol. 13, 305–309.PubMedGoogle Scholar
  32. Ellis, J. & Bernstein, A. (1989) Mol. Cell. Biol. 9, 1621–1627.PubMedGoogle Scholar
  33. Esumi, N., Hunt, B., Itaya, T. & Frost, P. (1991) Cancer Res. 51, 1185–1189.PubMedGoogle Scholar
  34. Fearon, E. R., Pardoll, D. M., Itaya, T., Golumbek, P., Levitsky, H. I., Simons, J. W., Karasuyama, H., Vogelstein, B. & Frosst, P. (1990 ) Cell 60, 397–403.PubMedGoogle Scholar
  35. Felgner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., Northrop, J. P., Ringold, G. M. & Danielson, M. (1987) Proc. Natl Acad. Sci. USA 84, 7413–7417.PubMedGoogle Scholar
  36. Fraley, R., Subramani, S., Berg, P. & Papahadjopoulos, D. (1980) J. Biol. Chem. 255,10431–10435.PubMedGoogle Scholar
  37. Friedmann, T. (1989) Science 244, 1275–1281.PubMedGoogle Scholar
  38. Friedmann, T. & Roblin, R. (1972) Science 178, 648–649.Google Scholar
  39. Frohman, M. A. & Martin, G. R. (1989) Cell 56, 145–147.PubMedGoogle Scholar
  40. Gage, F. H., Wolff, J. A., Rosenberg, M. B., Xu, L., Yee, J.-K., Shults, C. & Friedmann, T. (1987) Neuroscience 23, 795–807.PubMedGoogle Scholar
  41. Gansbacher, B., Zier, K., Daniels, B., Cronin, K., Bannerji, R. & Gilboa, E. (1990) J. Exp. Med. 172, 1217–1224.PubMedGoogle Scholar
  42. Gebara, M. M., Drevon, C., Harcourt, S. A., Steingrimsdottir, H., James, M. R., Burke, J. F., Arlett, C. F. & Lehmann, A. R. (1987) Mol. Cell. Biol. 7, 1459–1464.PubMedGoogle Scholar
  43. Geller, A. I. & Breakefield, X. O. (1988) Science 241, 1667–1669.PubMedGoogle Scholar
  44. Ghattas, I. R., Sanes, J. R. & Majors, J. E. (1991) Mol. Cell. Biol. 11, 5848–5859.PubMedGoogle Scholar
  45. Golumbeck, P. T., Lazenby, A. J., Levitsky, H. I., Jaffee, L. M., Karasuyama, H., Baker, M. & Pardoll, D. M. (1991) Science 254, 713–716.Google Scholar
  46. Graham, F. L. & van der Eb, A. J. (1973) Virology 52, 456–467.PubMedGoogle Scholar
  47. Günzburg, W. H. & Salmons, B. (1986) Virology 155, 236–248.PubMedGoogle Scholar
  48. Guild, B. C., Mulligan, R. C., Gros, P. & Housman, D. E. (1988) Proc. Natl Acad. Sci. USA 85, 1595–1599.PubMedGoogle Scholar
  49. Hamada, K., Akagi, T., Okano, A., Taki, S., Shimotohno, K. & Takahara, V. (1991) Immunol. Methods 141,177–186.Google Scholar
  50. Hefti, F. & Weiner, W. J. (1988) Ann. Neurol. 20, 275–281.Google Scholar
  51. Hollstein, M., Sidransky, D., Vogelstein, B. & Harris, C. C. (1991) Science 253, 49–53.PubMedGoogle Scholar
  52. Huang, H.-J. S., Yee, J.-K., Shew, J.-Y., Chen, P-L., Bookstein, R., Friedmann, T., Lee, E. Y.-H. P. & Lee, W.-H. (1988) Science 242, 1563–1566.PubMedGoogle Scholar
  53. Jähner, D. and Jaenisch, R. (1985) Nature 315, 594–597.PubMedGoogle Scholar
  54. Johnson, P. A., Miyanohara, A., Levine, F., Cahill, T. & Friedmann, T. (1992) J. Virol. 66, 2952–2965.PubMedGoogle Scholar
  55. Jolly, D. J., Willis, R. C. & Friedmann, T. (1986) Mol. Cell. Biol. 6, 1141–1147.PubMedGoogle Scholar
  56. Kaneda, Y., Iwai, K. & Uchida, T. (1989) Science 243, 375–378.PubMedGoogle Scholar
  57. Kantoff, P. W., Gillio, A. P., McLachlin, J. R., Bordignon, C., Eglitis, M. A., Kernan, N. A., Moen, R. C., Kohn, D. B., Yu, S. F., Karson, E., Karlsson, S., Zwiebel, J. A., Gilboa, E., Blaese, R. M., Nienhuis, A., O’Reilly, R. J. & Anderson, W. F. (1987) J. Exp. Med. 166, 219–234.PubMedGoogle Scholar
  58. Kasid, A., Morecki, S., Aebersold, P., Cornetta, K., Culver, K., Freeman, S., Director, E., Lotze, M. T., Blaese, R. M. & Anderson, W. F. (1990) Proc. Natl Acad. Sci. USA 87, 413–411 . Google Scholar
  59. Keating, A. & Toneguzzo, F. (1990) Prog. Clin. Biol. Res. 333, 491–498.PubMedGoogle Scholar
  60. Keller, G., Paige, C., Gilboa, E. & Wagner, E. F. (1985) Nature 318, 149–154.PubMedGoogle Scholar
  61. Klein, T. M., Wolf, E. D., Wu, R. & Sanford, J. C. (1987) Nature 327, 70–73.Google Scholar
  62. Kolberg, R. (1992) J. NIH Res. 4, 43–44.Google Scholar
  63. Kwong, A. D. & Frenkel, N. (1984) J. Virol. 51, 595–603.PubMedGoogle Scholar
  64. Laker, C., Stocking, C., Bergholz, U., Hess, N., DeLamarter, J. F. & Ostertag, W. (1987) Proc. Natl Acad. Sci. USA 84, 8458–8462.PubMedGoogle Scholar
  65. Lebkowski, J. S., McNally, M. M., Okarma, T. B. & Lerch, L. B. (1988) Mol. Cell. Biol. 8, 3988–3996.PubMedGoogle Scholar
  66. Levine, F., Yee, J. K. & Friedmann, T. (1991) Gene (Amst.) 108, 167–174.Google Scholar
  67. Lindvall, O., Brundin, P., Widner, H., Rehncrona, S., Gustavii, B., Frackowiak, R., Leenders, K., Sawle, G., Rothwell, J., Marsden, D. & Bjorklund, A. (1989) Science 247, 574–577.Google Scholar
  68. Longnecker, R., Roizman, B. & Meignier, B. (1988) Viral vectors (Gluzman, Y. & Hughes, S. H., eds) pp. 67–72, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.Google Scholar
  69. Lynch, C. M., Clowes, M. M., Osborne, W. R. A., Clowes, A. W. & Miller, A. D. (1992) Proc. Natl Acad. Sci. USA 89, 1138–1142.PubMedGoogle Scholar
  70. Magli, M. C., Dick, J. E., Huszar, D., Bernstein, A. & Phillips, R. A. (1987) Proc. Natl Acad. Sci. USA 84, 789–793.PubMedGoogle Scholar
  71. Martuza, R. L., Malick, A., Markert, J. M., Ruffner, K. L. & Coen, D. M. (1991) Science 252, 854–856.PubMedGoogle Scholar
  72. McBride, O. W. & Ozer, H. L. (1973) Proc. Natl Acad. Sci. USA 70, 1258–1262.PubMedGoogle Scholar
  73. McKusick, V. A. (1988) Mendelian inheritance in man, 8th edn, Johns Hopkins University Press, Baltimore.Google Scholar
  74. McLachlin, J. R., Cornetta, K., Eglitis, M. A. & Anderson, W. F. (1990) Prog. Nucleic Acid Res. Mol. Biol. 38, 91–135.Google Scholar
  75. Miller, A. D. & Buttimore, C. (1986) Mol. Cell. Biol. 6, 2895–2902.PubMedGoogle Scholar
  76. Miyanohara, A., Sharkey, M. F., Witztum, J. L, Steinberg, D. & Friedmann, T. (1988) Proc. Natl Acad. Sci. USA 85, 6538–6542.PubMedGoogle Scholar
  77. Miyanohara, A., Elam, R. L., Witztum, J. L. & Friedmann, T. (1992a) New Biol. 4, 261–267.PubMedGoogle Scholar
  78. Miyanohara, A., Johnson, P. A., Elam, R. L., Dai, Y., Witztum, J. L., Verma, I. M. & Friedmann, T. (1992b) New Biol. 4, 238–246.PubMedGoogle Scholar
  79. Moss, B. & Flexner, C. (1987) Annu. Rev. Immunol. 5, 305–327.PubMedGoogle Scholar
  80. Nabel, E. G., Plautz, G., Boyce, F. M., Stanley, J. C. & Nabel, G. J. (1989) Science 244, 1342–1344.PubMedGoogle Scholar
  81. Novak, U., Harris, E. A. S., Forrester, W., Groudine, M. & Gelinas, R. (1990) Proc. Natl Acad. Sci. USA 87, 3386–3390.PubMedGoogle Scholar
  82. O’Gorman, S., Fox, D. T. & Wahl, G. M. (1991) Science 251,1351–1355.PubMedGoogle Scholar
  83. Pagano, J., McCutchan, J. H. & Vaheri, A. (1967) J. Virol. 1, 891–897.PubMedGoogle Scholar
  84. Palmer, T. D., Rosman, G. J., Osborne, W. R. A. & Miller, A. D. (1991) Proc. Natl Acad. Sci. USA 88,1330–1334.PubMedGoogle Scholar
  85. Panning, B. & Smiley, J. R. (1989) J. Virol. 63, 1929–1937.PubMedGoogle Scholar
  86. Peng, H., Armentano, D., MacKenzie-Graham, L., Shen, R.-F., Darlington, G., Ledley, F. D. & Woo, S. L. C. (1988) Proc. Natl Acad. Sci. USA 85, 8146–8150.PubMedGoogle Scholar
  87. Ponder, K., Gupta, S., Leland, F., Darlington, G., Finegold, M., DeMayo, J., Ledley, F. D., Chowdhury, J. R. & Woo, S. L. C. (1991) Proc. Natl Acad. Sci. USA 88, 1217–1221.PubMedGoogle Scholar
  88. Rich, D. P., Anderson, M. P., Gregory, R. J., Cheng, S. H., Paul, S., Jefferson, D. M., McCann, J. D., Klinger, K. W., Smith, A. E. & Welsh, M. J. (1990) Nature 347, 358–363.PubMedGoogle Scholar
  89. Riordan, J. R., Rommens, J. M., Kerem, B.-S., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsik, N., Chou, J.-L., Drumm, M. L., Iannuzzi, M. C., Collins, F. S. & Tsui, L.-C. (1989) Science 245, 1066–1072.PubMedGoogle Scholar
  90. Roemer, K., Johnson, P. A. & Friedmann, T. (1991) J. Virol. 65, 6900–6912.PubMedGoogle Scholar
  91. Roemer, K., Johnson, P. A. & Friedmann, T. (1992) J. Gen. Virol. 73, 1553–1558.PubMedGoogle Scholar
  92. Roman, M., Axelrod, J. H., Dai, Y., Naviaux, R. K., Friedmann, T. & Verma, I. M. (1992)Somatic Cell Mol. Genet., in the press.Google Scholar
  93. Rosenberg, M. B., Friedmann, T., Robertson, R. C., Tuszynski, M., Wolff, J. A., Breakefield, X. O. & Gage, F. H. (1988) Science 242, 1575–1578.PubMedGoogle Scholar
  94. Rosenberg, S. A., Aebersold, P., Cornetta, K., Kasaid, A., Morgan, R. A., Moen, R., Karson, E. M., Lotze, M. T., Yang, J. C. & Topalian, S. L. (1990) N. Engl. J. Med. 323, 570–578.PubMedGoogle Scholar
  95. Rosenfeld, M. A., Siegfried, W., Yoshimura, K., Yoneyama, K., Fukayama, M., Stier, L., Pääkkö, P. K., Gilardi, P., Stratford- Perricaudet, L. D., Perricaudet, M., Jallat, S., Pavirani, A., Lecocq, J.-P. & Crystal, R. G. (1991) Science 252, 431–434.PubMedGoogle Scholar
  96. Schaffner, W. (1980) Proc. Natl Acad. Sci. USA 77, 2163–2168.PubMedGoogle Scholar
  97. Scharfmann, R., Axelrod, J. H. & Verma, I. M. (1991) Proc. Natl Acad. Sci. USA 88, 4626–4630.PubMedGoogle Scholar
  98. Shigekawa, K. and Dower, W. J. (1988) Biotechniques 6, 742–751.PubMedGoogle Scholar
  99. Shih, C.-C., Stoye, J. P. & Coffin, J. M. (1988) Cell 53, 531–537.PubMedGoogle Scholar
  100. Sklar, M. D., Thompson, E., Welsh, M. J., Liebert, M., Harney, J., Grossman, H. B., Smith, M. & Prochownik, E. V. (1991) Mol. Cell. Biol. 11, 3699–3710.PubMedGoogle Scholar
  101. Sorge, J. & Hughes, S. H. (1982) J. Mol. Appl. Genet. 1, 547–559.PubMedGoogle Scholar
  102. Spandidos, D. A. & Siminovitch, L. (1977) Proc. Natl Acad. Sci. USA 74, 3480–3484.PubMedGoogle Scholar
  103. Spangrude, G. J., Heimfeld, S. & Weissman, I. L. (1988) Science 241, 58–62.PubMedGoogle Scholar
  104. St. Louis, D. & Verma, I. M. (1988) Proc. Natl Acad. Sci. USA 85, 3150–3154.Google Scholar
  105. Stanbridge, E. J. (1976) Nature 260,17–20.PubMedGoogle Scholar
  106. Stanley, C., Rosenberg, M. B. & Friedmann, T. (1991) Somatic Cell Mol. Genet. 17,185–190.Google Scholar
  107. Stead, R. B., Kwok, W. W., Storb, R. & Miller, A. D. (1988) Blood 71, 142–141 . Google Scholar
  108. Stief, A., Winter, D. M., Strätling, W. H. & Sippel, A. E. (1989) Nature 341, 343–345.PubMedGoogle Scholar
  109. Stratford-Perricaudet, L., Levrero, M., Chasse, J.-F., Perricaudet, M. & Briand, P. (1990) Hum. Gene Ther. 1, 241–256.PubMedGoogle Scholar
  110. Sugawa, H., Uchida, T., Yoneda, Y., Ishiura, M. & Okada, Y. (1985) Exp. Cell Res. 159, 410–418.PubMedGoogle Scholar
  111. Top, F. H. Jr, Buescher, E. L., Bancroft, W. H. & Russell, P. K. (1971) J. Infect. Dis. 124, 155–160.PubMedGoogle Scholar
  112. Ueda, K., Cardarelli, C., Gottesman, M. M. & Pastan, I. (1987) Proc. Natl Acad. Sci. USA 84, 3004–3008.PubMedGoogle Scholar
  113. Van Beusechem, V. W., Kukler, A., Bakx, T. A. & Valerio, D. (1989) Bone Marrow Transplant. 4, 133–136PubMedGoogle Scholar
  114. Varmus, H. E. (1982) Science 216, 812–820.PubMedGoogle Scholar
  115. Varmus, H. (1988) Science 240, 1427–1435.PubMedGoogle Scholar
  116. Volsky, D. J., Gross, T., Sinangil, F., Kuszynski, C., Bartzatt, R., Dambaugh, T. & Kieff, E. (1984) Proc. Natl Acad. Sci. USA 81, 5926–5930.PubMedGoogle Scholar
  117. Watanabe, Y. (1980) Atherosclerosis 36, 261–268.PubMedGoogle Scholar
  118. Weinberg, R. A. (1991) Science 254, 1138–1146.PubMedGoogle Scholar
  119. Williams, D. A., Orkin, S. H. & Mulligan, R. C. (1986) Proc. Natl Acad. Sci. USA 83, 2566–2570.PubMedGoogle Scholar
  120. Wilson, J. M., Jefferson, D. M., Chowdhury, J. R., Novikoff, P. M., Johnston, D. E. & Mulligan, R. C. (1988) Proc. Natl Acad. Sci. USA 85, 3014–3018.PubMedGoogle Scholar
  121. Wolff, J. A., Yee, J.-K., Skelly, H. F., Moores, J. C., Respess, J. G., Friedmann, T. & Leffert, H. (1987) Proc. Natl Acad. Sci. USA 84, 3344–3348.PubMedGoogle Scholar
  122. Wolff, J. A., Fisher, L. J., Xu, L., Jinnah, H. A., Langlais, P. J., Iuovone, P. M., O’Malley, K. L., Rosenberg, M. B., Shimohama, S., Friedmann, T. & Gage, F. H. (1989) Proc. Natl Acad. Sci. USA 86, 9011–9014.PubMedGoogle Scholar
  123. Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A. & Feigner, P. (1990) Science 247, 1465–1468.PubMedGoogle Scholar
  124. Wu, G. Y., Wilson, J. M., Shalaby, F., Grossman, M., Shafritz, D. A. & Wu, C. H. (1991) Biol. Chem. 266, 14338–14342.Google Scholar
  125. Xu, L., Yee, J.-K., Wolff, J. A. & Friedmann, T. (1989) Virology 171, 331–341.PubMedGoogle Scholar
  126. Yee, J.-K., Moores, J. C., Jolly, D. J., Wolff, J. A., Respess, J. G. & Friedmann, T. (1987) Proc. Natl Acad. Sci. USA 84, 5197–5201.PubMedGoogle Scholar
  127. Young, J. A. T., Bates, P., Willert, K. & Varmus, H. E. (1990) Science 250, 1421–1423.PubMedGoogle Scholar
  128. Yu, S. F., von Rüden, T., Kantoff, P. W., Garber, C., Seiberg, M., Ruther, U., Anderson, W. F., Wagner, E. F. & Gilboa, E. (1986) Proc. Natl Acad. Sci. USA 83, 3194–3198PubMedGoogle Scholar

Copyright information

© Federation of European Biochemical Societies 1993

Authors and Affiliations

  • Klaus Roemer
    • 1
  • Theodore Friedmann
    • 1
  1. 1.Center for Molecular GeneticsUniversity of CaliforniaSan DiegoUSA

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