Nucleic-acid therapeutics: Basic principles and recent applications

Nature Reviews Drug Discovery

Volumn 1, Issue 7, 2002, Pages 503-514

  Opalinska, Joanna B ^a   Gewirtz, Alan M ^b  

^a POMERANIAN MEDICAL UNIVERSITY   (Poland)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOZYME; ANTISENSE OLIGODEOXYNUCLEOTIDE; ANTIVIRUS AGENT; CGP 69846A; CIDOFOVIR; CORTICOSTEROID; CYCLIC AMP DEPENDENT PROTEIN KINASE; DACARBAZINE; DNA; FOMIVIRSEN; FOSCARNET; GANCICLOVIR; GENE EXPRESSION MODULATOR 231; INTERCELLULAR ADHESION MOLECULE 1; ISIS 2503; ISIS 3521; LEXITROPSIN; MESSENGER RNA; MITOXANTRONE; OBLIMERSEN; PROTEIN BCL 2; PROTEIN C MYB; PROTEIN KINASE C ALPHA; RAF PROTEIN; RAS PROTEIN; RIBOZYME; SOMATOMEDIN C RECEPTOR; TRANSCRIPTION FACTOR; UNINDEXED DRUG; VASCULOTROPIN RECEPTOR 1; ANTISENSE OLIGONUCLEOTIDE; DEOXYRIBOZYME;

ADVANCED CANCER; APOPTOSIS; B CELL LYMPHOMA; BREAST CANCER; CLINICAL TRIAL; COLON CANCER; CROHN DISEASE; GENE EXPRESSION; GENE MUTATION; GENE SEQUENCE; GENE SILENCING; GENE TARGETING; GENE THERAPY; GENETIC TRANSCRIPTION; HEMATOLOGIC MALIGNANCY; HUMAN; HUMAN GENOME; INTRACORONARY INFUSION; LUNG NON SMALL CELL CANCER; MOLECULAR GENETICS; NONHODGKIN LYMPHOMA; ONCOGENE C MYB; ONCOGENE H RAS; PRIORITY JOURNAL; RETINITIS; REVIEW; RNA SPLICING; RNA TRANSLATION; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION; SOLID TUMOR; DRUG EFFECT; ONCOGENE MYB;

APOPTOSIS; CLINICAL TRIALS; DNA, CATALYTIC; GENE EXPRESSION; GENE SILENCING; GENES, MYB; HUMANS; OLIGONUCLEOTIDES, ANTISENSE; RNA SPLICING; RNA, CATALYTIC; SIGNAL TRANSDUCTION;

EID: 0036636074     PISSN: 14741776     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrd837     Document Type: Review

References (148)

1. Vile, R. G., Russell, S. J. & Lemoine, N. R. Cancer gene therapy: hard lessons and new courses. Gene Ther. 7, 2-8 (2000).
2. Gewirtz, A. M., Sokol, D. L. & Ratajczak, M. Z. Nucleic acid therapeutics: state of the art and future prospects. Blood 92, 712-736 (1998).
3. Mann, M. J. et al. Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomised, controlled trial. Lancet 354, 1493-1498 (1999).
4. Ehsan, A., Mann, M, J., Dell'Acqua, G. & Dzau, V. J. Long-term stabilization of vein graft wall architecture and prolonged resistance to experimental atherosclerosis after E2F decoy oligonucleotide gene therapy. J. Thorac. Cardiovasc. Surg. 121, 714-722 (2001).
5. Dean, N. M., McKay, R., Condon, T. P. & Bennett, C. F. Inhibition of protein kinase C-α expression in human A549 cells by antisense oligonucleotides inhibits induction of intercellular adhesion molecule 1 (ICAM-1) mRNA by phorbol esters. J. Biol. Chem. 269, 16416-16424 (1994).
6. Yacyshyn, B. R. et al. A placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn's disease. Gastroenterology 114, 1133-1142 (1998).
7. Macpherson, J. L., Ely, J. A., Sun, L. Q. & Symonds, G. P. Ribozymes in gene therapy of HIV-1. Front. Biosci. 4, D497-D505 (1999).
8. Welch, P. J., Yei, S. & Barber, J. R. Ribozyme gene therapy for hepatitis C virus infection. Clin. Diagn. Virol. 10, 163-171 (1998).
9. Zu Putlitz, J., Yu, Q., Burke, J. M. & Wands, J. R. Combinatorial screening and intracellular antiviral activity of hairpin ribozymes directed against hepatitis B virus. J. Virol. 73, 5381-5387 (1999).
10. Compagno, D. et al. Antisense oligonucleotides containing modified bases inhibit in vitro translation of Leishmania amazonensis mRNAs by invading the mini-exon hairpin. J. Biol. Chem. 274, 8191-8198 (1999).
11. Katz, S. M. et al. Effect of ICAM-1/LFA-1 blockade on pancreatic islet allograft survival, function, and early cytokine production. Transplant. Proc. 29, 748-749 (1997).
12. Gewirtz, A. M. Oligonucleotide therapeutics: a step forward. J. Clin. Oncol. 18, 1809-1811 (2000).
13. Paterson, B. M., Roberts, B. E. & Kuff, E. L. Structural gene identification and mapping by DNA-mRNA hybrid-arrested cell-free translation. Proc. Natl Acad. Sci. USA 74, 4370-4374 (1977).
14. Stephenson, M. L. & Zamecnik, P. C. Inhibition of Rous sarcoma viral RNA translation by a specific oligodeoxyribonucleotide. Proc. Natl Acad. Sci. USA 75, 285-288 (1978).
15. Simons, R. W. & Kleckner, N. Translational control of IS10 transposition. Cell 34, 683-691 (1983).
16. Mizuno, T., Chou, M. Y. & Inouye, M. A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). Proc. Natl Acad. Sci. USA 81, 1966-1970 (1984).
17. Melton, D. W. Gene targeting in the mouse. Bioessays 16, 633-638 (1994).
18. Stasiak, A. Getting down to the core of homologous recombination. Science 272, 828-829 (1996).
19. Helene, C. Control of oncogene expression by antisense nucleic acids. Eur. J. Cancer 30A, 1721-1726 (1994).
20. Knauert, M. P. & Glazer, P. M. Triplex forming oligonucleotides: sequence-specific tools for gene targeting. Hum. Mol. Genet. 10, 2243-2251 (2001).
21. Luo, Z., Macris, M. A., Faruqi, A. F. & Glazer, P. M. High-frequency intrachromosomal gene conversion induced by triplex-forming oligonucleotides microinjected into mouse cells. Proc. Natl Acad. Sci. USA 97, 9003-9008 (2000).
22. Gamper, H. B. et al. The DNA strand of chimeric RNA/DNA oligonucleotides can direct gene repair/conversion activity in mammalian and plant cell-free extracts. Nucleic Acids Res. 28, 4332-4339 (2000).
23. Sharma, H. W., Perez, J. R., Higgins-Sochaski, K., Hsiao, R. & Narayanan, R. Transcription factor decoy approach to decipher the role of NF-κB in oncogenesis. Anticancer Res. 16, 61-69 (1996).
24. Kielkopf, C. L., Baird, E. E., Dervan, P. B. & Rees, D. C. Structural basis for G•C recognition in the DNA minor groove. Nature Struct. Biol. 5, 104-109 (1998).
25. Kielkopf, C. L. et al. A structural basis for recognition of A•T and T•A base pairs in the minor groove of B-DNA. Science 282, 111-115 (1998).
26. Kielkopf, C. L. et al. Structural effects of DNA sequence on T•A recognition by hydroxypyrrole/pyrrole pairs in the minor groove. J. Mol. Biol. 295, 557-567 (2000).
27. Urbach, A. R. & Dervan, P. B. Toward rules for 1:1 polyamide:DNA recognition. Proc. Natl Acad. Sci. USA 98, 4343-4348 (2001).
28. Beelman, C. A. & Parker, R. Degradation of mRNA in eukaryotes. Cell 81, 179-183 (1995).
29. Liebhaber, S. A. mRNA stability and the control of gene expression. Nucleic Acids Symp. Ser. 36, 29-32 (1997).
30. Weiss, I. M. & Liebhaber, S. A. Erythroid cell-specific mRNA stability elements in the α2-globin 3′ nontranslated region. Mol. Cell. Biol. 15, 2457-2465 (1995).
31. Chkheidze, A. N. et al. Assembly of the α-globin mRNA stability complex reflects binary interaction between the pyrimidine-rich 3′ untranslated region determinant and poly(C) binding protein αCP. Mol. Cell. Biol. 19, 4572-4581 (1999).
32. Scanlon, K. J. et al. Oligonucleotide-mediated modulation of mammalian gene expression. FASEB J. 9, 1288-1296 (1995).
33. Stein, C. A. How to design an antisense oligodeoxynucleotide experiment: a consensus approach. Antisense Nucleic Acid Drug Dev. 8, 129-132 (1998).
34. Kole, R. & Sazani, P. Antisense effects in the cell nucleus: modification of splicing. Curr. Opin. Mol. Ther. 3, 229-234 (2001).
35. Dominski, Z. & Kole, R. Identification and characterization by antisense oligonucleotides of exon and intron sequences required for splicing. Mol. Cell. Biol. 14, 7445-7454 (1994).
36. Summerton, J. & Weller, D. Morpholino antisense oligomers: design, preparation, and properties. Antisense Nucleic Acid Drug Dev. 7, 187-195 (1997).
37. Iversen, P. L. Phosphorodiamidate morpholino oligomers: favorable properties for sequence-specific gene inactivation. Curr. Opin. Mol. Ther. 3, 235-238 (2001).
38. Zamaratski, E., Pradeepkumar, P. I. & Chattopadhyaya, J. A critical survey of the structure-function of the antisense oligo/RNA heteroduplex as substrate for RNase H. J. Biochem. Biophys. Methods 48, 189-208 (2001).
39. Crooke, S. T. Molecular mechanisms of antisense drugs: RNase H. Antisense Nucleic Acid Drug Dev. 8, 133-134 (1998).
40. Castanotto, D., Scherr, M. & Rossi, J. J. Intracellular expression and function of antisense catalytic RNAs. Methods Enzymol. 313, 401-420 (2000).
41. Rossi, J. J. Ribozymes, genomics and therapeutics. Chem. Biol. 6, R33-R37 (1999).
42. Santoro, S. W. & Joyce, G. F. A general purpose RNA-cleaving DNA enzyme. Proc. Natl Acad. Sci. USA 94, 4262-4266 (1997).
43. Wu, Y. et al. Inhibition of BCR-ABL oncogene expression by novel deoxyribozymes (DNAzymes). Hum. Gene Ther. 10, 2847-2857 (1999).
44. Earnshaw, D. J. & Gait, M. J. Progress toward the structure and therapeutic use of the hairpin ribozyme. Antisense Nucleic Acid Drug Dev. 7, 403-411 (1997).
45. Hampel, A. The hairpin nbozyme: discovery, two-dimensional model, and development for gene therapy. Prog. Nucleic Acid Res. Mol. Biol. 58, 1-39 (1998).
46. Dahm, S. C. & Uhlenbeck, O. C. Role of divalent metal ions in the hammerhead RNA cleavage reaction. Biochemistry 30, 9464-9469 (1991).
47. Eckstein, F. The hammerhead ribozyme. Biochem. Soc. Trans. 24, 601-604 (1996).
48. Hegg, L. A. & Fedor, M. J. Kinetics and thermodynamics of intermolecular catalysis by hairpin ribozymes. Biochemistry 34, 15813-15828 (1995).
49. Hertel, K. J., Herschlag, D. & Uhlenbeck, O. C. A kinetic and thermodynamic framework for the hammerhead ribozyme reaction. Biochemistry 33, 3374-3385 (1994).
50. Irie, A. et al. Anti-oncogene ribozymes for cancer gene therapy. Adv. Pharmacol. 40, 207-257 (1997).
51. Irie, A. et al. Therapeutic efficacy of an adenovirus-mediated anti-H-Ras ribozyme in experimental bladder cancer. Antisense Nucleic Acid Drug Dev. 9, 341-349 (1999).
52. Datta, H. J. & Glazer, P. M. Intracellular generation of single-stranded DNA for chromosomal triplex formation and induced recombination. Nucleic Acids Res. 29, 5140-5147 (2001).
53. Usman, N. & Blatt, L. M. Nuclease-resistant synthetic ribozymes: developing a new class of therapeutics. J. Clin. Invest. 106, 1197-1202 (2000).
54. Breaker, R. R. & Joyce, G. F. A DNA enzyme that cleaves RNA. Chem. Biol. 1, 223-229 (1994).
55. Feldman, A. R. & Sen, D. A new and efficient DNA enzyme for the sequence-specific cleavage of RNA. J. Mol. Biol. 313, 283-294 (2001).
56. Sioud, M. Nucleic acid enzymes as a novel generation of anti-gene agents. Curr. Mol. Med. 1, 575-588 (2001).
57. Nishikura, K. A short primer on RNAi: RNA-directed RNA polymerase acts as a key catalyst. Cell 107, 415-418 (2001).
58. Tuschl, T. Expanding small RNA interference. Nature Biotechnol. 20, 446-448 (2002).
59. Elbashir, S. M., Lendeckel, W. & Tuschl, T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 15, 188-200 (2001).
60. Bernstein, E., Caudy, A. A., Hammond, S. M. & Hannon, G. J. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409, 363-366 (2001).
61. Hammond, S. M., Boettcher, S., Caudy, A. A., Kobayashi, R. & Hannon, G. J. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 293, 1146-1150 (2001).
62. Ketting, R. F. et al. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 15, 2654-2659 (2001).
63. Yang, S., Tutton, S., Pierce, E. & Yoon, K. Specific double-stranded RNA interference in undifferentiated mouse embryonic stem cells. Mol. Cell. Biol. 21, 7807-7816 (2001).
64. Paddison, P. J., Caudy, A. A. & Hannon, G. J. Stable suppression of gene expression by RNAi in mammalian cells. Proc. Natl Acad. Sci. USA 99, 1443-1448 (2002).
65. Bernstein, E., Denli, A. M. & Hannon, G. J. The rest is silence. RNA 7, 1509-1521 (2001).
66. Yang, D., Lu, H. & Erickson, J. W. Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos. Curr. Biol. 10, 1191-1200 (2000).
67. Zamore, P. D., Tuschl, T., Sharp, P. A. & Bartel, D. P. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101, 25-33 (2000).
68. Elbashir, S. M., Martinez, J., Patkaniowska, A., Lendeckel, W. & Tuschl, T. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J. 20, 6877-6888 (2001).
69. Sierakowska, H., Sambade, M. J., Agrawal, S. & Kole, R. Repair of thalassemic human β-globin mRNA in mammalian cells by antisense oligonucleotides. Proc. Natl Acad. Sci. USA 93, 12840-12844 (1996).
70. Sierakowska, H., Agrawal, S. & Kole, R. Antisense oligonucleotides as modulators of pre-mRNA splicing. Methods Mol. Biol. 133, 223-233 (2000).
71. Lacerra, G. et al. Restoration of hemoglobin A synthesis in erythroid cells from peripheral blood of thalassemic patients. Proc. Natl Acad. Sci. USA 97, 9591-9596 (2000).
72. Mercatante, D. R., Bortner, C. D., Cidlowski, J. A. & Kole, R. Modification of alternative splicing of Bcl-x pre-mRNA in prostate and breast cancer cells. analysis of apoptosis and cell death. J. Biol. Chem. 276, 16411-16417 (2001).
73. Agrawal, S. & Zhao, Q. Mixed backbone oligonucleotides: improvement in oligonucleotide-induced toxicity in vivo. Antisense Nucleic Acid Drug Dev. 8, 135-139 (1998).
74. Crooke, S. T. Molecular mechanisms of action of antisense drugs. Biochim. Biophys. Acta 1489, 31-44 (1999).
75. Stein, C. A. Is irrelevant cleavage the price of antisense efficacy? Pharmacol. Ther. 85, 231-236 (2000).
76. Nielsen, P. E. DNA analogues with nonphosphodiester backbones. Annu. Rev. Biophys. Biomol. Struct. 24, 167-183 (1995).
77. Wong-Staal, F., Poeschla, E. M. & Looney, D. J. A controlled, Phase I clinical trial to evaluate the safety and effects in HIV-1 infected humans of autologous lymphocytes transduced with a ribozyme that cleaves HIV-1 RNA. Hum. Gene Ther. 9, 2407-2425 (1998).
78. + hematopoietic progenitor cells transduced with an anti-HIV ribozyme. Hum. Gene Ther. 10, 2255-2270 (1999).
79. Sereni, D. et al. Pharmacokinetics and tolerability of intravenous trecovirsen (GEM 91), an antisense phosphorothioate oligonucleotide, in HIV positive subjects. J. Clin. Pharmacol. 39, 47-54 (1999).
80. Bishop, M. R. et al. Phase I trial of an antisense oligonucleotide OL(1)p53 in hematologic malignancies. J. Clin. Oncol. 14, 1320-1326 (1996).
81. Galbraith, W. M., Hobson, W. C., Giclas. P. C.. Schechter, P. J. & Agrawal, S. Complement activation and hemodynamic changes following intravenous administration of phosphorothioate oligonucleotides in the monkey. Antisense Res. Dev. 4, 201-206 (1994).
82. Nemunaitis, J. et al. Phase I evaluation of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C-α, in patients with advanced cancer. J. Clin. Oncol. 17, 3586-3595 (1999).
83. Waters, J. S. et al. Phase I clinical and pharmacokinetic study of BCL2 antisense oligonucleotide therapy in patients with non-Hodgkin's lymphoma. J. Clin. Oncol. 18, 1812-1823 (2000).
84. Chi, K. N. et al. A Phase I dose-finding study of combined treatment with an antisense Bcl2 oligonucleotide (Genasense) and mitoxantrone in patients with metastatic hormone-refractory prostate cancer. Clin. Cancer Res. 7, 3920-3927 (2001).
85. Yuen, A. R. et al. Phase I study of an antisense oligonucleotide to protein kinase C-α (ISIS 3521/CGP 64128A) in patients with cancer. Clin. Cancer Res. 5, 3357-3363 (1999).
86. Yang, E. & Korsmeyer, S. J. Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood 88, 386-401 (1996).
87. Reed, J. C. Bcl2 family proteins: regulators of chemoresistance in cancer. Toxicol. Lett. 82-83, 155-158 (1995).
88. Gazitt, Y. et al. Bcl-2 overexpression is associated with resistance to paclitaxel, but not gemcitabine, in multiple myeloma cells. Int. J. Oncol. 13, 839-848 (1998).
89. Reed, J. C. et al. Antisense-mediated inhibition of BCL2 protooncogene expression and leukemic cell growth and survival: comparisons of phosphodiester and phosphorothioate oligodeoxynucleotides. Cancer Res. 50, 6565-6570 (1990).
90. Webb, A. et al. BCL-2 antisense therapy in patients with non-Hodgkin lymphoma. Lancet 349, 1137-1141 (1997).
91. Jansen, B. et al. Chemosensitisation of malignant melanoma by BCL2 antisense therapy. Lancet 356, 1728-1733 (2000).
92. Tolcher, A. W. Preliminary phase I results of G3139 (Bcl2 antisense oligonucleotide) therapy in combination with docetaxel in hormone-refractory prostate cancer. Semin. Oncol. 28, 67-70 (2001).
93. Luger, S. M. et al. Oligodeoxynucleotide-mediated inhibition of c-myb gene expression in autografted bone marrow: a pilot study. Blood 99, 1150-1158 (2002).
94. Dean, N. M. et al. Antisense oligonucleotides as inhibitors of signal transduction: development from research tools to therapeutic agents. Biochem. Soc. Trans. 24, 623-629 (1996).
95. Dean, N. et al. Inhibition of growth of human tumor cell lines in nude mice by an antisense of oligonucleotide inhibitor of protein kinase C-α expression. Cancer Res. 56, 3499-3507 (1996).
96. Cunningham, C. C. et al. A Phase I trial of H-ras antisense oligonucleotide ISIS 2503 administered as a continuous intravenous infusion in patients with advanced carcinoma. Cancer 92, 1265-1271 (2001).
97. Brennscheidt, U. et al. Raf-1 is a necessary component of the mitogenic response of the human megakaryoblastic leukemia cell line MO7 to human stem cell factor, granulocyte-macrophage colony-stimulating factor, interleukin 3, and interleukin 9. Cell Growth Differ. 5, 367-372 (1994).
98. Monia, B. P., Johnston, J. F., Geiger, T., Muller, M. & Fabbro, D. Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase. Nature Med. 2, 668-675 (1996).
99. Rudin, C. M. et al. Phase I trial of ISIS 5132, an antisense oligonucleotide inhibitor of c-raf-1, administered by 24-hour weekly infusion to patients with advanced cancer. Clin. Cancer Res. 7, 1214-1220 (2001).
100. Eckstein, F. Exogenous application of ribozymes for inhibiting gene expression. Ciba Found. Symp. 209, 207-212 (1997).
101. Looney, D. & Yu, M. Clinical aspects of ribozymes as therapeutics in gene therapy. Methods Mol. Biol. 74, 469-486 (1997).
102. Brower, V. et al. All clear for HIV-targeting ribozyme in Phase II. Nature Biotechnol. 16, 123 (1998).
103. Bennett, C. F., Condon, T. P., Grimm, S., Chan, H. & Chiang, M. Y. Inhibition of endothelial cell adhesion molecule expression with antisense oligonucleotides. J. Immunol. 152, 3530-3540 (1994).
104. Nestle, F. O., Mitra, R. S., Bennett, C. F., Chan, H. & Nickoloff, B. J. Cationic lipid is not required for uptake and selective inhibitory activity of ICAM-1 phosphorothioate antisense oligonucleotides in keratinocytes. J. Invest. Dermatol. 103, 569-575 (1994).
105. Miele, M. E., Bennett, C. F., Miller, B. E. & Welch, D. R. Enhanced metastatic ability of TNF-α-treated malignant melanoma cells is reduced by intercellular adhesion molecule-1 (ICAM-1, CD54) antisense oligonucleotides. Exp. Cell Res. 214, 231-241 (1994).
106. Schreiber, S. et al. Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn's disease. Gastroenterology 120, 1339-1346 (2001).
107. Wraight, C. J. et al. Reversal of epidermal hyperproliferation in psoriasis by insulin-like growth factor I receptor antisense oligonucleotides. Nature Biotechnol. 18, 521-526 (2000).
108. Roque, F. et al. Safety of intracoronary administration of c-myc antisense oligomers after percutaneous transluminal coronary angioplasty (PTCA). Antisense Nucleic Acid Drug Dev. 11, 99-106 (2001).
109. Kutryk, M. J. et al. Local intracoronary administration of antisense oligonucleotide against c-myc for the prevention of in-stent restenosis: results of the randomized investigation by the Thoraxcenter of antisense DNA using local delivery and IVUS after coronary stenting (ITALICS) trial. J. Am. Coll. Cardiol. 39, 281-287 (2002).
110. Krieg, A. M. et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374, 546-549 (1995).
111. Krug, A. et al. Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12. Eur J. Immunol. 31, 3026-3037 (2001).
112. H1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice. Proc. Natl Acad. Sci. USA 95, 15553-15558 (1998).
113. Krieg, A. M., Yi, A. K., Schorr, J. & Davis, H. L, The role of CpG dinucleotides in DNA vaccines. Trends Microbiol. 6, 23-27 (1998).
114. Jahrsdorfer, B, et al. CpG DNA increases primary malignant B cell expression of costimulatory molecules and target antigens. J. Leukoc. Biol. 69, 81-88 (2001).
115. Methia, N., Louache, F., Vainchenker, W. & Wendling, F. Oligodeoxynucleotides antisense to the proto-oncogene c-mpl specifically inhibit in vitro megakaryocytopoiesis. Blood 82, 1395-1401 (1993).
116. Good, L., Awasthi, S. K,, Dryselius, R., Larsson, O. & Nielsen, P. E. Bactericidal antisense effects of peptide-PNA conjugates. Nature Biotechnol. 19, 360-364 (2001).
117. Meshorer, E. et al. Alternative splicing and neuritic mRNA translocation under long-term neuronal hypersensitivity. Science 295, 508-512 (2002).
118. Andrews, D. W. et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J. Clin. Oncol. 19, 2189-2200 (2001).
119. Cunningham, C. C. et al. A Phase I trial of c-Raf kinase antisense oligonucleotide ISIS 5132 administered as a continuous intravenous infusion in patients with advanced cancer. Clin. Cancer Res. 6, 1626-1631 (2000).
120. Gewirtz, A. M., Stein, C. A. & Glazer, P. M. Facilitating oligonucleotide delivery: helping antisense deliver on its promise. Proc. Natl Acad. Sci, USA 93, 3161-3163 (1996).
121. Lebedeva, I. & Stein, C. A. Antisense oligonucleotides: promise and reality. Annu. Rev. Pharmacol. Toxicol. 41, 403-419 (2001).
122. Baskerville, S. & Ellington, A. D. RNA structure. Describing the elephant. Curr. Biol. 5, 120-123 (1995).
123. Monia, B. P. et al. Sequence-specific antitumor activity of a phosphorothioate oligodeoxyribonucleotide targeted to human C-raf kinase supports an antisense mechanism of action in vivo. Proc. Natl Acad. Sci. USA 93, 15481-15484 (1996).
124. Sczakiel, G., Homann, M. & Rittner, K. Computer-aided search for effective antisense RNA target sequences of the human immunodeficiency virus type 1. Antisense Res. Dev. 3, 45-52 (1993).
125. Milner, N., Mir, K. U. & Southern, E. M. Selecting effective antisense reagents on combinational oligonucleotide arrays. Nature Biotechnol. 15, 537-541 (1997).
126. Sohail, M. & Southern, E. M. Selecting optimal antisense reagents. Adv. Drug Deliv. Rev. 44, 23-34 (2000).
127. Ho, S. P. et al. Mapping of RNA accessible sites for antisense experiments with oligonucleotide libraries. Nature Biotechnol. 16, 59-63 (1998).
128. Scherr, M., Rossi, J. J., Sczakiel, G. & Patzel, V. RNA accessibility prediction: a theoretical approach is consistent with experimental studies in cell extracts. Nucleic Acids Res. 28, 2455-2461 (2000).
129. Sokol, D. L., Zhang, X., Lu, P. & Gewirtz, A. M. Real time detection of DNA. RNA hybridization in living cells. Proc. Natl Acad. Sci. USA 95, 11538-11543 (1998).
130. Yakubov, L. A. et al. Mechanism of oligonucleotide uptake by cells: involvement of specific receptors? Proc. Natl Acad. Sci. USA 86, 6454-6458 (1989).
131. Beltinger, C. et al. Binding, uptake, and intracellular trafficking of phosphorothioate-modified oligodeoxynucleotides. J. Clin. Invest. 95, 1814-1823 (1995).
132. Laktionov, P. et al. Uptake of oligonucleotides by keratinocytes. Nucleosides Nucleotides 18, 1697-1699 (1999).
133. Mechti, N., Leonetti, J. P., Clarenc, J, P., Degols, G. & Lebleu, B. Nuclear location of synthetic oligonucleotides microinjected somatic cells: its implication in an antisense strategy. Nucleic Acids Symp. Ser. 147-150 (1991).
134. Clarenc, J. P., Lebleu, B. & Leonetti, J. P. Characterization of the nuclear binding sites of oligodeoxyribonucleotides and their analogs. J. Biol. Chem. 268, 5600-5604 (1993).
135. Juliano, R. L,, Alahari, S., Yoo, H., Kole, R. & Cho, M. Antisense pharmacodynamics: critical issues in the transport and delivery of antisense oligonucleotides. Pharm. Res. 16, 494-502 (1999).
136. DeLong, R. K. et al. Novel cationic amphiphiles as delivery agents for antisense oligonucleotides. Nucleic Acids Res. 27, 3334-3341 (1999).
137. Baer, M. R., Augustinos, P. & Kinniburgh, A. J. Defective c-myc and c-myb RNA turnover in acute myeloid leukemia cells. Blood 79, 1319-1326 (1992).
138. Bies, J., Nazarov, V. & Wolff, L. Alteration of proteolytic processing of c-Myb as a consequence of its truncation in murine myeloid leukemia. Leukemia 13, S116-S117 (1999).
139. Kitada, S., Miyashita T., Tanaka, S, & Reed, J. C. Investigations of antisense oligonucleotides targeted against Bcl2 RNAs. Antisense Res. Dev. 3, 157-169 (1993).
140. Mandiyan, S. et al. Molecular and cellular characterization of baboon c-Raf as a target for antiproliferative effects of antisense oligonucleotides. Antisense Nucleic Acid Drug Dev. 7, 539-548 (1997).
141. Haklai, R. et al. Dislodgment and accelerated degradation of Ras. Biochemistry 37, 1306-1314 (1998).
142. Basilion, J. P. et al. Selective killing of cancer cells based on loss of heterozygosity and normal variation in the human genome: a new paradigm for anticancer drug therapy. Mol. Pharmacol. 56, 359-369 (1999).
143. Stein, C. A. Does antisense exist? Nature Med. 1, 1119-1121 (1995).
144. De Smet, M. D., Meenken, C. J. & van den Horn, G. J. Fomivirsen - a phosphorothioate oligonucleotide for the treatment of CMV retinitis. Ocul. Immunol. Inflamm. 7, 189-198 (1999).
145. Mulamba, G. B., Hu, A., Azad, R. F., Anderson, K. P. & Coen, D. M. Human cytomegalovirus mutant with sequence-dependent resistance to the phosphorothioate oligonucleotide fomivirsen. Antimicrob. Agents Chemother. 42, 971-973 (1998).
146. Anderson, K. P., Fox, M. C., Brown-Driver, V., Martin, M. J. & Azad, R. F. Inhibition of human cytomegalovirus immediate-early gene expression by an antisense oligonucleotide complementary to immediate-early RNA. Antimicrob. Agents Chemother. 40, 2004-2011 (1996).
147. The Vitravene Study Group. A randomized controlled clinical trial of intravitreous Fomiversen for treatment of newly diagnosed peripheral cytomegalovirus retinitis in patients with AIDs. Am. J. Opthalmol. 133, 467-474 (2002).
148. Coudert, B. et al. Phase II with ISIS 5132 in patients with small-cell (SCLC) and non-small-cell (NSCLC) lung cancer. A European Organization for Research and Treatment of Cancer (EORTC) early clinical studies group report. Eur. J. Cancer 37, 2194-2198 (2001).