Critical Considerations and Future Directions

  • Martin R Bennett
  • Stephen M Schwartz
Part of the Perspectives in Antisense Science book series (DARE, volume 3)


The upsurge in interest in the use of antisense agents to inhibit restenosis reflects the poor results of clinical trials of conventional agents to affect the restenosis rates. At present, over 12 oligonucleotides are in clinical trials, for a variety of diseases. To examine whether this interest in antisense agents for restenosis is warranted, it is first necessary to analyse the advantages of antisense agents over conventional therapies, and to consider shortfalls in our knowledge of both the disease process, and the use of antisense agents in vivo, both of which wil limit the applicability of this technology to human disease.


Target mRNA Antisense Oligonucleotide Antisense Oligodeoxynucleotides Antisense Sequence Phosphorothioate Oligonucleotide 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Wang, A, Creasy, A, Lardner, M, Lin, L, Strickler, J, Van Arsdell, J, Yamamoto, R and Mark, D. Molecular cloning of the complementary DNA for human tumor necrosis factor. Science. 1985; 228:149–154.PubMedCrossRefGoogle Scholar
  2. 2.
    Holt, J T, Redner, R L and Nienhuis, A W. An oligomer complementary to c-myc mRNA inhibits proliferation of HL-60 promyelocytic cells and induces differentiation. Mol Cell Biol.1988; 8:963–973.PubMedGoogle Scholar
  3. 3.
    Bennett, M R, Anglin, S, McEwan, J R, Jagoe, R, Newby, A C and Evan, G I. Inhibition of vascular smooth muscle cell proliferation in vitro and in vivo by c-myc antisense oligodeoxynucleotides. J Clin Invest. 1994; 93:820–828.PubMedCrossRefGoogle Scholar
  4. 4.
    Saison, B T, Tocqu’e, B, Rey, I, Chassignol, M, Thuong, N T and H’elene, C. Short modified antisense oligonucleotides directed against Ha-ras point mutation induce selective cleavage of the mRNA and inhibit T24 cells proliferation. Embo J.1991; 10:1111–1118.Google Scholar
  5. 5.
    Gao, W Y, Storm, C, Egan, W and Cheng, Y C.Cellular pharmacology of phosphorothioate homooligodeoxynucleotides in human cells. Mol Pharmacol.1993; 43:45–50.PubMedGoogle Scholar
  6. 6.
    Muller, R, Mumberg, D and Lucibello, F C. Signals and genes in the control of cell-cycle progression. Biochim Biophys Acta.1993; 1155:151–179.PubMedGoogle Scholar
  7. 7.
    Waller, B F, Pinkerton, C A, Orr, C M, Slack, J D, VanTassel, J W and Peters, T. Restenosis 1 to 24 months after clinically successful coronary balloon angioplasty: a necropsy study of 20 patients. J Am Coll Cardiol.1991; 17(Suppl B):58B–70B.PubMedCrossRefGoogle Scholar
  8. 8.
    Mintz, G, Popma, J, Pichard, A, Kent, K, Satler, L, Wong, S, Hong, M, Kovach, J and Leon, M. Arterial remodeling after coronary angioplasty. A serial intravascular ultrasound study. Circulation. 1996; 94:35–43.PubMedCrossRefGoogle Scholar
  9. 9.
    Shi, Y, Pieniek, M, Fard, A, O’Brien, J, Mannion, J and Zalewski, A. Adventitial remodeling after coronary arterial injury. Circulation. 1996; 93:340–348.PubMedCrossRefGoogle Scholar
  10. 10.
    Shi, Y, O’Brien, J, Ala-Kokko, L, Chung, W, Mannion, J and Zalewski, A. Origin of extracellular matrix synthesis during coronary repair. Circulation. 1997; 95:1997.Google Scholar
  11. 11.
    Lewin, B.Genes. In, (ed. 1990, Oxford University Press, New YorkGoogle Scholar
  12. 12.
    Kozak, M. Influences of mRNA secondary structure on initiation by eucaryotic ribosomes. Proc Natl Acad Sci USA. 1986; 83:2850–2854.PubMedCrossRefGoogle Scholar
  13. 13.
    Chiang, M Y, Chan, H, Zounes, M A, Freier, S M, Lima, W F and Bennett, C F. Antisense oligonucleotides inhibit intercellular adhesion molecule 1 expression by two distinct mechanisms. J Biol Chem.1991; 266:18162–18171.PubMedGoogle Scholar
  14. 14.
    Abe, J, Zhou, W, Taguchi, J, Takuwa, N, Miki, K, Okazaki, H, Kurokawa, K, Kumada, M and Takuwa, Y.Suppression of neointimal smooth muscle cell accumulation in vivo by antisense cdc2 and cdk2 oligonucleotides in rat carotid artery. Biochem Biophys Res Commun. 1994; 198:16–24.PubMedCrossRefGoogle Scholar
  15. 15.
    Crooke, R. In vitro toxiciology and pharacokinetics of antisense oligonucleotides. Anti-Cancer Drug Design. 1991; 6:609–646.PubMedGoogle Scholar
  16. 16.
    Kitajima, I, Shinohara, T, Minor, T, Bibbs, L, Bilakovics, J and Nerenberg, M. Human T-cell leukemia virus type I tax transformation is associated with increased uptake of oligodeoxynucleotides in vitro and in vivo. J Biol Chem.1992; 267:25881–25888.PubMedGoogle Scholar
  17. 17.
    Yakubov, L A, Deeva, E A, Zarytova, V F, Ivanova, E M, Ryte, A S, Yurchenko, L V and Vlassov, V V. Mechanism of oligonucleotide uptake by cells: involvement of specific receptors? Proc Natl Acad Sci USA. 1989; 86:6454–6458.PubMedCrossRefGoogle Scholar
  18. 18.
    Stein, C A, Tonkinson, J L, Zhang, L M, Yakubov, L, Gervasoni, J, Taub, R and Rotenberg, S A. Dynamics of the intemalization of phosphodiester oligodeoxynucleotides in HL60 cells. Biochemistry. 1993; 32:4855–4861.PubMedCrossRefGoogle Scholar
  19. 19.
    Spiller, D G and Tidd, D M. The uptake kinetics of chimeric oligodeoxynucleotide analogues in human leukaemia MOLT-4 cells. Anticancer Drug Des.1992; 7:115–129.PubMedGoogle Scholar
  20. 20.
    Juliano, R L and Akhtar, S. Liposomes as a drug delivery system for antisense oligonucleotides. Antisense Res Dev.1992; 2:165–176.PubMedGoogle Scholar
  21. 21.
    Clarenc, J P, Degols, G, Leonetti, J P, Milhaud, P and Lebleu, B. Delivery of antisense oligonucleotides by poly(L-lysine) conjugation and liposome encapsulation. Anticancer Drug Des.1993; 8:81–94.PubMedGoogle Scholar
  22. 22.
    Loke, S, Stein, C, Zhang, X, Avigan, M, Cohen, J and Neckers, L. Delivery of c-myc antisense phosphorothioate oligodeoxynucleotides to haemopoietic cells in culture by liposome fusion: specific reduction in c-myc protein expression correlates with inhibition of cell growth and DNA synthesis. Curr Top Microbiol Immunol.1988; 141:282–289.PubMedCrossRefGoogle Scholar
  23. 23.
    Bennett, C F, Chiang, M Y, Chan, H, Shoemaker, J E and Mirabelli, C K. Cationic lipids enhance cellular uptake and activity of phosphorothioate antisense oligonucleotides. Mol Pharmacol. 1992; 41:1023–1033.PubMedGoogle Scholar
  24. 24.
    Capaccioli, S, Di Pasquale, G, Mini, E, Mazzei, T and Quattrone, A. Cationic lipids improve antisense oligonucleotide uptake and prevent degradation in cultured cells and in human serum. Biochem Biophys Res Commun. 1993; 197:818–825.PubMedCrossRefGoogle Scholar
  25. 25.
    Morishita, R, Gibbons, G H, Ellison, K E, Nakajima, M, Zhang, L, Kaneda, Y, Ogihara, T and Dzau, V J. Single intraluminal delivery of antisense cdc2 kinase and proliferating-cell nuclear antigen oligonucleotides results in chronic inhibition of neointimal hyperplasia. Proc Natl Acad Sci U S A. 1993; 90:8474–8478.PubMedCrossRefGoogle Scholar
  26. 26.
    Morishita, R, Gibbons, G H, Ellison, K E, Nakajima, M, von, d L H, Zhang, L, Kaneda, Y, Ogihara, T and Dzau, V J. Intimai hyperplasia after vascular injury is inhibited by antisense cdk 2 kinase oligonucleotides. J Clin Invest. 1994; 93:1458–1464.PubMedCrossRefGoogle Scholar
  27. 27.
    Citro, G, Perrotti, D, Cucco, C, D’Agnano, I, Sacchi, A, Zupi, G and Calabretta, B. Inhibition of leukemia cell proliferation by receptor-medrated uptake of c-myb antisense oligodeoxynucleotides. Proc Natl Acad Sci U S A. 1992; 89:7031–7035.PubMedCrossRefGoogle Scholar
  28. 28.
    Daum, T, Engels, J W, Mag, M, Muth, J, Lucking, S, Schroder, H C, Matthes, E and Muller, W E. Antisense oligodeoxynucleotide: inhibitor of splicing of mRNA of human immunodeficiency virus. Intervirology. 19920; 33:65–75.PubMedGoogle Scholar
  29. 29.
    Shi, Y, Hutchison, H, Hall, D and Zalewsky, A. Downregulation of c-myc expression by antisense oligonucleotides inhibits proliferation of human smooth muscle cells. Circulation. 1993; 88:1190–1195.PubMedCrossRefGoogle Scholar
  30. 30.
    Simons, M, Edelman, E R, DeKeyser, J L, Langer, R and Rosenberg, R D. Antisense c-myb oligonucleotides inhibit arterial smooth muscle cell accumulation in vivo. Nature. 1992; 359:67–70.PubMedCrossRefGoogle Scholar
  31. 31.
    Shi, Y, Fard, A, Galeo, A, Hutchinson, H G, Vermani, P, Dodge, G R, Hall, D J, Shaheen, F and Zalewski, A. Transcatheter delivery of c-myc antisense oligomers reduces neointimal formation in a porcine model of coronary artery balloon injury. Circulation. 1994; 90:944–951.PubMedCrossRefGoogle Scholar
  32. 32.
    Wickstrom, E L, Bacon, T A, Gonzalez, A, Freeman, D L, Lyman, G H and Wickstrom, E. Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA. Proc Natl Acad Sci U S A. 1988; 85:1028–1032.PubMedCrossRefGoogle Scholar
  33. 33.
    Wickstrom, E. Oligonucleotide stability in subcellular extracts and culture media. J Biochem Biophys Meth.1986; 13:97–102.PubMedCrossRefGoogle Scholar
  34. 34.
    Uhlmann, E and Peyman, A. Antisense oligonucleotides. A new therapeutic principle. Chemical Reviews. 1990; 90:544.CrossRefGoogle Scholar
  35. 35.
    van der Krol, A, Mol, J and Stuitje, A. Modulation of eukaryotic gene expression by complementary RNA or DNA sequences. Biotechniques. 1988; 6(10):958–976.PubMedGoogle Scholar
  36. 36.
    Marcus-Sekura, C, Woemer, A, Shinozuka, K, Zon, G and Quinnan, G. Comparative inhibition of chloramphenicol acetyltransferase gene expression by antisense oligonucleotide analogues having alkyl triester, methyl phosphonate and phosphorothioate linkages. Nucl Acid Res.1987; 15:5749–5763.CrossRefGoogle Scholar
  37. 37.
    Cazenave, C, Stein, C, Loreau, N, Thuong, N, Neckers, L, Subasinghe, C, H’elene, C, Cohen, J and Toulm’e, J. Comparative inhibition of rabbit globin mRNA translation by modified antisense oligodeoxynucleotides. Nucleic Acids Res.1989; 17(11):4255–4273.PubMedCrossRefGoogle Scholar
  38. 38.
    Hoke, G, Draper, K, Freier, S, Gonzalez, C, Driver, V, Zounes, M and Ecker, D. Effects of phosphorothioate capping on antisense oligonucleotide stability, hybridization and antiviral., efficacy versus herpes simplex virus infec. Nucleic Acids Res.1991; 19(20:5743–5748.PubMedCrossRefGoogle Scholar
  39. 39.
    Maher, L J 3 and Dolnick, B J.Comparative hybrid arrest by tandem antisense oligodeoxyribonucleotides or oligodeoxyribonucleoside methylphosphonates in a cell-free system. Nucleic Acids Res.1988; 16:3341–3358.PubMedCrossRefGoogle Scholar
  40. 40.
    Ghosh, M K, Ghosh, K and Cohen, J S. Translation inhibition by phosphorothioate oligodeoxynucleotides in cell-free systems. Antisense Res Dev.1992; 2:111–118.PubMedGoogle Scholar
  41. 41.
    Stein, C and Cohen, J. Phosphorothioate oligonucleotide analogues. In, Antisense inhibitors of gene expression (ed. J. Cohen), 1989, CRC Press, Boca Raton, FL., pp97.Google Scholar
  42. 42.
    Reed, J, Stein, C, Subasinghe, C, Haldar, S, Croce, C, Yum, S and Cohen, J. Antisense-mediated inhibition of BCL2 protooncogene expression and leukemic cell growth and survival: comparisons of phosphodiester and phosphorothioate oligodeoxynucleotides. Cancer-Res.1990; 50(20):6565–6570.PubMedGoogle Scholar
  43. 43.
    Daaka, Y and Wickstrom, E. Target dependence of antisense oligodeoxynucleotide inhibition of c-Ha-ras p21 expression and focus formation in T24-transformed NIH3T3 cells. Oncogene Res.1990; 5(4):267–275.PubMedGoogle Scholar
  44. 44.
    Rosolen, A, Whitesell, L, Ikegaki, N, Kennett, R H and Neckers, L M. Antisense inhibition of single copy N-myc expression results in decreased cell growth without reduction of c-myc protein in a neuroepithelioma cell line. Cancer Res.1990; 50:6316–6322.PubMedGoogle Scholar
  45. 45.
    H’elene, C.The anti-gene strategy: control of gene expression by triplex-forming-oligonucleotides. Anticancer Drug Des.1991; 6:569–584.Google Scholar
  46. 46.
    Postel, E.H. Modulation of c-myc transcription by triple helix formation. Ann N Y Acad Sci.1992; 660:57–63.PubMedCrossRefGoogle Scholar
  47. 47.
    Grigoriev, M, Praseuth, D, Guieysse, A L, Robin, P, Thuong, N T, H’elene, C and Harel, B A. Inhibition of gene expression by triple helix-directed DNA cross-linking at specific sites. Proc Natl Acad Sci USA. 1993; 90:3501–3505.PubMedCrossRefGoogle Scholar
  48. 48.
    Miller, P and Tso, P. Anew approach to chemotherapy based on molecular biology and nucleic acid chemistry: Matagen (masking tape for gene expression). Anti Cancer Drug Design. 1987; 2:117–128.PubMedGoogle Scholar
  49. 49.
    Woolf, T M, Melton, D A and Jennings, C G B. Specificity of antisense oligonucleotides in vivo. Proc Natl Acad Sci USA. 1992; 89:7305–7309.PubMedCrossRefGoogle Scholar
  50. 50.
    Donis-Keller, H. Site-specific cleavage of RNA. Nucl Acids Res.1979; 7:179–192.PubMedCrossRefGoogle Scholar
  51. 51.
    Shuttleworth, J, Mathews, G, Dale, L, Baker, C and Colman, A. Antisense oligodeoxynucleotide-directed cleavage of maternal mRNA in Xenopus oocytes and embryos. Gene.1988; 72:267–275.PubMedCrossRefGoogle Scholar
  52. 52.
    Dagle, J M, Weeks, D L and Walder, J A. Pathways of degradation and mechanism of action of antisense oligonucleotides in Xenopus laevis embryos. Antisense Res Dev.1991; 1:11–20.PubMedGoogle Scholar
  53. 53.
    Cazenave, C, Loreau, N, Thuong, N, Toulme, J J and Helene, C. Enzymatic amplification of translation inhibtion of rabbit β; globin mRNA mediated by antimessenger oligonucleotides covalently linked to intercalating agents. Nucl Acids Res.1987; 15:4717–4736.PubMedCrossRefGoogle Scholar
  54. 54.
    Giles, R V and Tidd, D M. Increased specificity for antisense oligodeoxynucleotide targeting of RNA cleavage by RNase H using chimeric methylphosphonodiester/phosphodiester structures. Nucleic Acids Res.1992; 20:763–770.PubMedCrossRefGoogle Scholar
  55. 55.
    Giles, R V, Spiller, D G and Tidd, D M. Chimeric oligodeoxynucleotide analogues: enhanced cell uptake of structures which direct ribonuclease H with high specificity. Anticancer Drug Des.1993; 8:33–51.PubMedGoogle Scholar
  56. 56.
    Lengyel, P. Biochemistry of interferons and their actions. Annu Rev Biochem. 1982; 51:251–282.PubMedCrossRefGoogle Scholar
  57. 57.
    Memet, S, Besancon, F, Bourgeade, M F and Thang, M N. Direct induction of interferon-gamma-and interferon-alpha/beta-inducible genes by double-stranded RNA. J Interferon Res.1991; 11:131–141.PubMedCrossRefGoogle Scholar
  58. 58.
    Hovanessian, A G. Interferon-induced and double-stranded RNA-activated enzymes: a specific protein kinase and 2′,5′-oligoadenylate synthetases. J Interferon Res.1991; 11:199–205.PubMedCrossRefGoogle Scholar
  59. 59.
    Hubbell, H R, Boyer, J E, Roane, P and Burch, R M. Cyclic AMP mediates the direct antiproliferative action of mismatched double-stranded RNA Proc Natl Acad Sci U S A. 1991; 88:906–910.PubMedCrossRefGoogle Scholar
  60. 60.
    Yaswen, P, Stampfer, M R, Ghosh, K and Cohen, J S. Effects of sequence of thioated oligonucleotides on cultured human mammary epithelial cells. Antisense Res Dev.1993; 3:67–77.PubMedGoogle Scholar
  61. 61.
    Garfinkel, S, Haines, D S, Brown, S, Wessendorf, J, Gillespie, D H and Maciag, T. Interleukin-1 alpha mediates an alternative pathway for the antiproliferative action of poly(I.C) on human endothelial cells. J Biol Chem.1992; 267:24375–24378.PubMedGoogle Scholar
  62. 62.
    Matsukura, M, Shinozuka, K, Zon, G, Mitsuya, H, Reitz, M, Cohen, J S and Broder, S. Phosphorothioate analogs of oligodeoxynucleotides: inhibitors of replication and cytopathic effects of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1987; 84:7706–7710.PubMedCrossRefGoogle Scholar
  63. 63.
    Bock, L C, Griffin, L C, Latham, J A, Vermaas, E H and Toole, J J. Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature. 1992; 355:564–566.PubMedCrossRefGoogle Scholar
  64. 64.
    Macaya, R F, Schultze, P, Smith, F W, Roe, J A and Feigon, J. Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution. Proc Natl Acad Sci U S A. 1993; 90:3745–3749.PubMedCrossRefGoogle Scholar
  65. 65.
    Griffin, L C, Tidmarsh, G F, Bock, L C, Toole, J J and Leung, L L. In vivo anticoagulant properties of a novel nucleotide-based thrombin inhibitor and demonstration of regional anticoagulation in extracorporeal circuits. Blood. 1993; 81:3271–3276.PubMedGoogle Scholar
  66. 66.
    Yakubov, L, Khaled, Z, Zhang, L M, Truneh, A, Vlassov, V and Stein, C A. Oligodeoxynucleotides interact with recombinant CD4 at multiple sites. J Biol Chem.1993; 268:18818–18823.PubMedGoogle Scholar
  67. 67.
    Ramanathan, M, MacGregor, R D and Hunt, C A. Predictions of effect for intracellular antisense oligodeoxyribonucleotides from a kinetic model. Antiseme Res Dev.1993; 3:3–18.Google Scholar
  68. 68.
    Morgan, R, Edge, M and Colman, A. A more efficient and specific strategy in the ablation of mRNA in Xenopus laevis using mixtures of antisense oligos. Nucleic Acids Res.1993; 21:4615–4620.PubMedCrossRefGoogle Scholar
  69. 69.
    Gao, W, Hanes, R N, Vazquez-Padua, M A, Stein, C A, Cohen, J S and Cheng, Y C. Inhibition oif herpes simplex virus type 2 growth by phosphorothiaote oligodeoxynucleotides. Antimicrobial Agents and Chemotherapy. 1990; 34:808–812.PubMedCrossRefGoogle Scholar
  70. 70.
    Woolf, T M, Jennings, C, Rebagliati, M and Melton-D-A. The stability, toxicity and effectiveness of unmodified and phosphorothioate antisense oligodeoxynucleotides in Xenopus oocytes and embryos. Nucleic Acids Res.1990; 18(7): 1763–1769.PubMedCrossRefGoogle Scholar
  71. 71.
    Gao, W Y, Han, F S, Storm, C, Egan, W and Cheng, Y C. Phosphorothioate oligonucleotides are inhibitors of human DNA polymerases and RNase H: implications for antisense technology. Mol Pharmacol. 1992; 41:223–229.PubMedGoogle Scholar
  72. 72.
    Komberg, A. Aspects of DNA replication. Cold Spring Harb Symp Quant Biol.1979.; 43 Pt 1:1–9.CrossRefGoogle Scholar
  73. 73.
    Bigelow, J C, Chrin, L R, Mathews, L A and McCormick, J J. High-performance liquid Chromatographic analysis of phosphorothioate analogues of oligodeoxynucleotides in biological fluids. J Chromatogr. 1990; 533:133–140.PubMedCrossRefGoogle Scholar
  74. 74.
    Agrawal., S, Temsamani, J and Tang, J Y. Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. Proc Natl Acad Sci U S A. 1991; 88:7595–7599.PubMedCrossRefGoogle Scholar
  75. 75.
    Iversen, P.In vivo studies with phosphorothioate oligonucleotides: pharmacokinetics prologue. Anticancer Drug Des.1991; 6:531–538.Google Scholar
  76. 76.
    Cazenave, C, Loreau, N, Toulm’e, J J and H’elene, C. Anti-messenger oligodeoxynucleotides: specific inhibition of rabbit beta-globin synthesis in wheat germ extracts and Xenopus oocytes. Biochimie. 1986; 68:1063–1069.PubMedCrossRefGoogle Scholar
  77. 77.
    Whitesell, L, Rosolen, A and Neckers, L M. In vivo modulation of N-myc expression by continuous perfusion with an antisense oligonucleotide. Antisense Res Dev.1991; 1:343–350.PubMedGoogle Scholar
  78. 78.
    Chiasson, B J, Hooper, M L, Murphy, P R and Robertson, H A. Antisense oligonucleotide eliminates in vivo expression of c-fos in mammalian brain. Eur J Pharmacol. 1992; 227:451–453.PubMedCrossRefGoogle Scholar
  79. 79.
    Amaratunga, A, Morin, P J, Kosik, K S and Fine, R E. Inhibition of kinesin synthesis and rapid anterograde axonal transport in vivo by an antisense oligonucleotide. J Biol Chem.1993; 268:17427–17430.PubMedGoogle Scholar
  80. 80.
    Whitesell, L, Geselowitz, D, Chavany, C, Fahmy, B, Walbridge, S, Alger, J R and Neckers, L M. Stability, clearance, and disposition of intraventricularly administered oligodeoxynucleotides: implications for therapeutic application within the central nervous system. Proc Natl Acad Sci U S A. 1993; 90:4665–4669.PubMedCrossRefGoogle Scholar
  81. 81.
    Citro, G, Ginobbi, P, Candiloro, A, Milani, A and Sarti, P. Chemical modification of ligands for cell receptors to introduce foreign compounds into the cells. Dis Colon Rectum. 1994; 37(2 Suppl):S127–S132.PubMedCrossRefGoogle Scholar
  82. 82.
    Lu, X M, Fischman, A J, Jyawook, S L, Hendricks, K, Tompkins, R G and Yarmush, M L. Antisense DNA delivery in vivo: liver targeting by receptor-mediated uptake. J Nucl Med.1994; 35:269–275.PubMedGoogle Scholar
  83. 83.
    Neckers, L, Rosolen, A, Fahmy, B and Whitesell, L. Specific inhibition of oncogene expression in vitro and in vivo by antisense oligonucleotides. Ann N Y Acad Sci.1992; 660:37–44.PubMedCrossRefGoogle Scholar
  84. 84.
    Riessen, R, Isner, J M, Blessing, E, Loushin, C, Nikol, S and Wight, T N. Regional differences in the distribution of the proteoglycans biglycan and decorin in the extracellular matrix of atherosclerotic and restenotic human coronary arteries. Am J Pathol.1994; 144:962–974.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Martin R Bennett
    • 1
  • Stephen M Schwartz
    • 2
  1. 1.Department of MedicineAddenbrooke’s HospitalCambridgeUK
  2. 2.Department of PathologyUniversity of WashingtonSeattleUSA

Personalised recommendations