The medicinal chemistry of oligonucleotides

Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition

Volumn , Issue , 2007, Pages 143-182

  Swayze, Eric E ^a   Bhat, Balkrishen ^a  

^a ISIS PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84894521728     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (242)

1. Limbach, P. A., Crain, P. F., and McCloskey, J. A., Summary: the modified nucleosides of RNA, Nucleic Acids Res., 22, 2183-2196, 1994.
2. Griffey, R. H., Sasmor, H., and Greig, M. J., Oligonucleotide charge states in negative ionization electrospray-mass spectrometry are a function of solution ammonium ion concentration, J. Am. Soc. Mass Spectrom., 8, 155-160, 1997.
3. Cohen, J. S., Informational drugs: a new concept in pharmacology, Antisense Res. Dev., 1, 191-193, 1991.
4. McKay, R. A. et al., Characterization of a potent and specific class of antisense oligonucleotide inhibitor of human protein kinase C-alpha expression, J. Biol. Chem., 274, 1715-1722, 1999.
5. Freier, S. M. and Altmann, K. H., The ups and downs of nucleic acid duplex stability: structure-stability studies on chemically-modified DNA:RNA duplexes, Nucleic Acids Res., 25, 4429-4443, 1997.
6. Crooke, S. T., Antisense Drug Technology, Marcel Dekker, New York, 2001, p. 929.
7. Eckstein, F., Phosphorothioate oligodeoxynucleotides: what is their origin and what is unique about them? Antisense Nucleic Acid Drug Dev., 10, 117-121, 2000.
8. Stein, C. A. et al., Physicochemical properties of phosphorothioate oligodeoxynucleotides, Nucleic Acids Res., 16, 3209-3221, 1988.
9. Geary, R. S., Yu, R. Z., and Levin, A. A., Pharmacokinetics of phosphorothioate antisense oligodeoxynucleotides, Curr. Opin. Investig. Drugs, 2, 562-573, 2001.
10. Stec, W. J., Stereocontrolled synthesis of P-chiral analogs of oligonucleotides, in Antisense Research and Applications, Crooke, S. T. and Lebleu, B. L., eds., CRC Press, Boca Raton, FL, 1993, pp. 251-271.
11. Guga, P. et al., Oligo(nucleosides phosphorothioate)s, in Applied Antisense Oligonucleotide Technology, Stein, C. A. and Krieg, A. M., eds., Wiley, New York, 1998, pp. 23-50.
12. Lu, Y., Recent advances in the stereocontrolled synthesis of antisense phosphorothioates, Mini Rev. Med. Chem., 6, 319-330, 2006.
13. Seeberger, P. H., Yau, E., and Caruthers, M. H., 2′-Deoxynucleoside dithiophosphates: synthesis and biological studies, J. Am. Chem. Soc., 117, 1472-1478, 1995.
14. Cummins, L. et al., Biochemical and physicochemical properties of phosphorodithioate DNA, Biochemistry, 35, 8734-8741, 1996.
15. Weisler, W. T. and Caruthers, M. H., Synthesis of phosphorodithioate DNA via sulfur-linked, baselabile protecting groups, J. Org. Chem., 61, 4272-4281, 1996.
16. Ghosh, M. K., Ghosh, K., and Cohen, J. S., Translation inhibition by phosphorothioate oligodeoxynucleotides in cell-free systems, Antisense Res. Dev., 2, 111-118, 1992.
17. Capaldi, D. C., Cole, D. L., and Ravikumar, V. T., Highly efficient solid phase synthesis of oligonucleotide analogs containing phosphorodithioate linkages, Nucleic Acids Res., 28, E40, 2000.
18. Spielvogel, B. F. et al., From boron analogues of amino acids to boronated DNA: potential new pharmaceuticals and neutron capture agents, Pure Appl. Chem., 63, 415, 1991.
19. Sood, A., Shaw, B. R., and Spiclvogel, B. F., Boron-containing nucleic acids. 2. Synthesis of oligodeoxynucleoside boranophosphates, J. Am. Chem. Soc., 112, 9000-9001, 1990.
20. Sergueev, D. S. and Shaw, B. R., H-Phosphonate approach for solid-phase synthesis of oligodeoxyribonucleoside boranophosphates and their characterization, J. Am. Chem. Soc., 120, 9417-9427, 1998.
21. Summers, J. S. and Shaw, B. R., Boranophosphates as mimics of natural phosphodiesters in DNA, Curr. Med. Chem., 8, 1147-1155, 2001.
22. Micklefield, J., Backbone modification of nucleic acids: synthesis, structure and therapeutic applications, Curr. Med. Chem., 8, 1157-1179, 2001.
23. Rait, V. et al., Boranophosphate nucleic acids-a versatile DNA backbone, Nucleos. Nucleot., 18, 1379-1380, 1999.
24. Rait, V. K. and Shaw, B. R., Boranophosphates support the RNase H cleavage of polyribonucleotides, Antisense Nucleic Acid Drug Dev., 9, 53-60, 1999.
25. Hall, A. H. et al., RNA interference using boranophosphate siRNAs: structure-activity relationships, Nucleic Acids Res., 32, 5991-6000, 2004.
26. Gryaznov, S. M. et al., Oligonucleotide N3′→P5′ phosphoramidates, Proc. Natl. Acad. Sci. USA, 92, 5798-5802, 1995.
27. Gryaznov, S. and Chen, J.-K., Oligodeoxyribonucleotide N3′→P5′ phosphoramidates: synthesis and hybridization properties, J. Am. Chem. Soc., 1994, 3143-3144, 1994.
28. Gryaznov, S. et al., Oligonucleotide N3′→P5′ phosphoramidates as antisense agents, Nucleic Acids Res., 24, 1508-1514, 1996.
29. Skorski, T. et al., Antileukemia effect of c-myc N3′→P5′ phosphoramidate antisense oligonucleotides in vivo, Proc. Natl. Acad. Sci. USA, 94, 3966-3971, 1997.
30. Faria, M. et al., Phosphoramidate oligonucleotides as potent antisense molecules in cells and in vivo, Nat. Biotechnol., 19, 40-44, 2001.
31. Pongracz, K. and Gryaznov, S., Oligonucleotide N3′→P5′ thiophosphoramidates: synthesis and properties, Tetrahedron Lett., 40, 7661-7664, 1999.
32. Wang, E. S. et al., Telomerase inhibition with an oligonucleotide telomerase template antagonist: in vitro and in vivo studies in multiple myeloma and lymphoma, Blood, 103, 258-266, 2004.
33. Herbert, B. S. et al., Lipid modification of GRN163, an N3′→P5′ thio-phosphoramidate oligonucleotide, enhances the potency of telomerase inhibition, Oncogene, 24, 5262-5268, 2005.
34. Dellinger, D. J. et al., Solid-phase chemical synthesis of phosphonoacetate and thiophosphonoacetate oligodeoxynucleotides, J. Am. Chem. Soc., 125, 940-950, 2003.
35. Yamada, C. M., Dellinger, D. M., and Caruthers, M. H., Synthesis and biochemical evaluation of phosphonoformate oligodeoxyribonucleotides, J. Amer. Chem. Soc., 128, 5251-5261, 2006.
36. Sheehan, D. et al., Biochemical properties of phosphonoacetate and thiophosphonoacetate oligodeoxyribonucleotides, Nucleic Acids Res., 31, 4109-4118, 2003.
37. Heinemann, U. et al., Effect of a single 3′-methylene phosphonate linkage on the conformation of an A-DNA octamer double helix, Nucleic Acids Res., 19, 427-433, 1991.
38. An, H. et al., Synthesis of novel 3′-C-methylene thymidine and 5-methyluridine/cytidine H-phosphonates and phosphonamidites for new backbone modification of oligonucleotides, J. Org. Chem., 66, 2789-2801, 2001.
39. Clark, R. E. et al., Clinical use of streptolysin-O to facilitate antisense oligodeoxyribonucleotide delivery for purging autografts in chronic myeloid leukaemia, Bone Marrow Transplant., 23, 1303-1308, 1999.
40. Hamma, T. and Miller, P. S., Interactions of hairpin oligo-2′-O-methylribonucleotides containing methylphosphonate linkages with HIV TAR RNA, Antisense Nucleic Acid Drug Dev., 13, 19-30, 2003.
41. Leberton, J. et al., Comparison of two amides as backbone replacement of the phosphodiester linkage in oligodeoxynucleotides, Tetrahedron Lett., 35, 5225-5228, 1994.
42. De Mesmaeker, A. et al., Amides as a new type of backbone modification in oligonucleotides, Angew. Chem. Int. Ed. Engl., 33, 226, 1994.
43. De Mesmaeker, A. et al., Amide backbones with conformationally restricted furanose rings: highly improved affinity of the modified oligonucleotides for their RNA complements, Angew. Chem. Int. Ed. Engl., 35, 2790-2794, 1996.
44. De Mesmaeker, A. et al., Amide-modified oligonucleotides with preorganized backbone and furanose rings: highly increased thermodynamic stability of the duplexes formed with their RNA and DNA complements, Synlett, 1287-1290, 1997.
45. Mafalda, N. et al., Recognition of RNA by amide modified backbone nucleic acids: molecular dynamics simulations of DNA-RNA hybrids in aqueous solution, J. Am. Chem. Soc., 127, 6027-6038, 2005.
46. Pallan, P. S. et al., RNA-binding affinities and crystal structure of oligonucleotides containing fiveatom amide-based backbone structures, Biochemistry, 45, 8048-8057, 2006.
47. Sanghvi, Y. S. et al., Concept, discovery and development of MMI linkage: story of a novel linkage for antisense constructs, Nucleos. Nucleot., 16, 907-916, 1997.
48. Peoc’h, D. et al., Synthesis of 2′-substituted MMI linked nucleosidic dimers: an optimization study in search of high affinity oligonucleotides for use in antisense constructs, Nucleos. Nucleot. Nucleic Acids, 23, 411-438, 2004.
49. Jones, R. J. et al., Synthesis and binding properties of pyrimidine oligodeoxynucleoside analogs containing neutral phosphodiester replacements: the formacetal and 3′-thioforplacetal internucleoside linkages, J. Org. Chem., 58, 2983-2991, 1993.
50. Zhang, J., Shaw, J. T., and Matteucci, M. D., Synthesis and hybridization property of an oligonucleotide containing a 3-thioformacetal linked pentathymidylate, Bioorg. Med. Chem. Lett., 9, 319-322, 1999.
51. Cross, C. W., Rice, J. S., and Gao, X., Solution structure of an RNA:DNA hybrid duplex containing a 3′-thioformacetal linker and an RNA A-tract, Biochemistry, 36, 4096-4107, 1997.
52. He, G. X. et al., In vitro and in vivo activities of oligodeoxynucleotide-based thrombin inhibitors containing neutral formacetal linkages, J. Med. Chem., 41, 4224-4231, 1998.
53. Sanghvi, Y. S. and Cook, P. D., Carbohydrate modifications in antisense research, Oxford University Press, Washington, D.C., 1994, p. 260.
54. Sanghvi, Y. S., DNA with altered backbones in antisense applications, in Comprehensive Natural Products Chemistry, Barton, D. H. R., Nakanishi, K., and Kool, E. T., eds., Pergamon Press, Oxford, 1999, pp. 258-311.
55. Kurreck, J., Antisense technologies. Improvement through novel chemical modifications, Eur. J. Biochem., 270, 1628-1644, 2003.
56. Alter, J. et al., Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology, Nat. Med., 12, 175-177, 2006.
57. Sazani, P. et al., Systemically delivered antisense oligomers upregulate gene expression in mouse tissues, Nat. Biotechnol., 20, 1228-1233, 2002.
58. Devi, G. R. et al., In vivo bioavailability and pharmacokinetics of a c-MYC antisense phosphorodiamidate morpholino oligomer, AVI-4126, in solid tumors, Clin. Cancer Res., 11, 3930-3938, 2005.
59. Summerton, J., Morpholino antisense oligomers: the case for an RNase H-independent structural type, Biochim. Biophys. Acta, 1489, 141-158, 1999.
60. Summerton, J. et al., Morpholino and phosphorothioate antisense oligomers compared in cell-free and in-cell systems, Antisense Nucleic Acid Drug Dev., 7, 63-70, 1997.
61. Summerton, J. and Weller, D., Morpholino antisense oligomers: design, preparation, and properties, Antisense Nucleic Acid Drug Dev., 7, 187-195, 1997.
62. Efimov, V. A. and Chakhmakhcheva, O. G., Synthesis of DNA mimics representing HypNA-pPNA hetero-oligomers, Methods Mol. Biol., 288, 147-164, 2005.
63. Efimov, V. A., Klykov, V. N., and Chakhmakhcheva, O. G., Phosphono peptide nucleic acids with a constrained hydroxyproline-based backbone, Nucleos. Nucleot. Nucleic Acids, 22, 593-599, 2003.
64. Efimov, V. A. et al., Hydroxyproline-based DNA mimics provide an efficient gene silencing in vitro and in vivo, Nucleic Acids Res., 34, 2247-2257, 2006.
65. Morris, M. C. et al., Combination of a new generation of PNAs with a peptide-based carrier enables efficient targeting of cell cycle progression, Gene Ther., 11, 757-764, 2004.
66. Egholm, M. et al., PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules, Nature, 365, 566-568, 1993.
67. Nielsen, P. E. et al., Sequence-selective recognition of DNA by strand displacement with a thyminesubstituted polyamide, Science, 254, 1497-1500, 1991.
68. Nulf, C. J. and Corey, D., Intracellular inhibition of hepatitis C virus (HCV) internal ribosomal entry site (IRES)-dependent translation by peptide nucleic acids (PNAs) and locked nucleic acids (LNAs), Nucleic Acids Res., 32, 3792-3798, 2004.
69. Doyle, D. F. et al., Inhibition of gene expression inside cells by peptide nucleic acids: effect of mRNA target sequence, mismatched bases, and PNA length, Biochemistry, 40, 53-64, 2001.
70. Siwkowski, A. M. et al., Identification and functional validation of PNAs that inhibit murine CD40 expression by redirection of splicing, Nucleic Acids Res., 32, 2695-2706, 2004.
71. Liu, B. et al., Transcription activation by a PNA-peptide chimera in a mammalian cell extract, Chem. Biol., 10, 909-916, 2003.
72. Janowski, B. A. et al., Inhibiting transcription of chromosomal DNA with antigene peptide nucleic acids, Nat. Chem. Biol., 1, 210-215, 2005.
73. Albertshofer, K. et al., Structure-activity relationship study on a simple cationic peptide motif for cellular delivery of antisense peptide nucleic acid, J. Med. Chem., 48, 6741-6749, 2005.
74. Maier, M. A. et al., Evaluation of basic amphipathic peptides for cellular delivery of antisense peptide nucleic acids, J. Med. Chem., 49, 2534-2542, 2006.
75. Haaima, G. et al., Peptide nucleic acids (PNAs) containing thymine monomers derived from chiral amino acids: hybridization and solubility properties of D-lysine PNA, Angew. Chem. Int. Ed., 35, 1939-1941, 1996.
76. Wancewicz, E. V. et al., Short basic peptides improve the pharmacokinetics and antisense activity of systemically delivered peptide nucleic acids, manuscript in preparation, 2007.
77. Altona, C. and Sundaralingam, M., Conformational analysis of the sugar ring in nucleosides and nucleotides. A new description using the concept of pseudorotation, J. Am. Chem. Soc., 94, 8205-8212, 1972.
78. Griffey, R. H. et al., New twists on nucleic acids: structural properties of modified nucleosides incorporated into oligonucleotides, in Carbohydrate Modifications in Antisense Research, Sanghvi, Y. S. and Cook, P. D., eds., Oxford University Press, Washington, D.C., 1994, pp. 212-224.
79. Ng, E. W. et al., Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease, Nat. Rev. Drug Discov., 5, 123-132, 2006.
80. Chiu, Y. L. and Rana, T. M., siRNA function in RNAi: A chemical modification analysis, RNA, 9, 1034-1048, 2003.
81. Morrissey, D. V. et al., Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication, Hepatology, 41, 1349-1356, 2005.
82. Morrissey, D. V. et al., Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs, Nat. Biotechnol., 23, 1002-1007, 2005.
83. Allerson, C. R. et al., Fully 2′-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA, J. Med. Chem., 48, 901-904, 2005.
84. Koller, E. et al., Competition for RISC binding predicts in vitro potency of siRNA, Nucl. Acids Res., gkl589, 2006.
85. Monia, B. P. et al., Evaluation of 2′-modified oligonucleotides containing 2′-deoxy gaps as antisense inhibitors of gene expression, J. Biol. Chem., 268, 14,514-14,522, 1993.
86. Kawasaki, A. M. et al., Uniformly modified 2′-deoxy-2′-fluoro phosphorothioate oligonucleotides as nuclease-resistant antisense compounds with high affinity and specificity for RNA targets, J. Med. Chem., 36, 831-841, 1993.
87. Damha, M. J. et al., Hybrids of RNA and arabinonucleic acids (ANA and 2′F-ANA) are substrates of ribonuclease H, J. Am. Chem. Soc., 120, 12,976-12,977, 1998.
88. Berger, I. et al., Crystal structures of B-DNA with incorporated 2′-deoxy-2′-fluoro-arabino-furanosyl thymines: implications of conformational preorganization for duplex stability, Nucleic Acids Res., 26, 2473-2480, 1998.
89. Li, F. et al., 2′-Fluoroarabino-and arabinonucleic acid show different conformations, resulting in deviating RNA affinities and processing of their heteroduplexes with RNA by RNase H, Biochemistry, 45, 4141-4152, 2006.
90. Lok, C.-N. et al., Potent gene-specific inhibitory properties of mixed-backbone antisense oligonucleotides comprised of 2′-deoxy-2′-fluoro-D-arabinose and 2′-deoxyribose nucleotides, Biochemistry, 41, 3457-3467, 2002.
91. Kalota, A. et al., 2′-deoxy-2′-fluoro-beta-D-arabinonucleic acid (2′F-ANA) modified oligonucleotides (ON) effect highly efficient, and persistent, gene silencing, Nucleic Acids Res., 34, 451-461, 2006.
92. Dowler, T. et al., Improvements in siRNA properties mediated by 2′-deoxy-2′-fluoro-beta-Darabinonucleic acid (FANA), Nucleic Acids Res., 34, 1669-1675, 2006.
93. Kraynack, B. A. and Baker, B. F., Small interfering RNAs containing full 2′-O-methylribonucleotidemodified sense strands display Argonaute2/eIF2C2-dependent activity, RNA, 12, 163-176, 2006.
94. Prakash, T. P. et al., Positional effect of chemical modifications on short interference RNA activity in Mammalian cells, J. Med. Chem., 48, 4247-4253, 2005.
95. Zimmermann, T. S. et al., RNAi-mediated gene silencing in non-human primates, Nature, 441, 111-114, 2006.
96. Soutschek, J. et al., Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs, Nature, 432, 173-178, 2004.
97. Jackson, A. L. et al., Position-specific chemical modification of siRNAs reduces “off-target” transcript silencing, RNA, 12, 1197-1205, 2006.
98. Fedorov, Y. et al., Off-target effects by siRNA can induce toxic phenotype, RNA, 12, 1188-1196, 2006.
99. Goel, S. et al., A phase I safety and dose escalation trial of docetaxel combined with GEM®231, a second generation antisense oligonucleotide targeting protein kinase A R1a in patients with advanced solid cancers, Invest. New Drugs, 24, 125-134, 2006.
100. Teplova, M. et al., Crystal structure and improved antisense properties of 2′-O-(2-methoxyethyl)-RNA, Nat. Struct. Biol., 6, 535-539, 1999.
101. Crooke, S. T. et al., Pharmacokinetic properties of several novel oligonucleotide analogs in mice, J. Pharmacol. Exp. Ther., 277, 923-937, 1996.
102. Prakash, T. P. et al., 2′-O-[2-(methylthio)ethyl]-modified oligonucleotide: an analogue of 2′-O-[2-(methoxy)-ethyl]-modified oligonucleotide with improved protein binding properties and high binding affinity to target RNA, Biochemistry, 41, 11,642-11,648, 2002.
103. Egli, M. et al., Probing the influence of stereoelectronic effects on the biophysical properties of oligonucleotides: comprehensive analysis of the RNA affinity, nuclease resistance, and crystal structure of ten 2′-O-ribonucleic acid modifications, Biochemistry, 44, 9045-9057, 2005.
104. Shen, L., Chen, X., and Wang, J. H., A high-efficacy antisense RIalpha poly-DNP 21-nt RNA, Antisense Nucleic Acid Drug Dev., 13, 67-74, 2003.
105. Chen, X., Shen, L., and Wang, J. H., Poly-2′-DNP-RNAs with enhanced efficacy for inhibiting cancer cell growth, Oligonucleotides, 14, 90-99, 2004.
106. Liao, H. and Wang, J. H., Biomembrane-permeable and Ribonuclease-resistant siRNA with enhanced activity, Oligonucleotides, 15, 196-205, 2005.
107. Shen, L. et al., Silencing of human c-myc oncogene expression by poly-DNP-RNA, Oligonucleotides, 15, 23-35, 2005.
108. Griffey, R. H. et al., 2′-O-aminopropyl ribonucleotides: a zwitterionic modification that enhances the exonuclease resistance and biological activity of antisense oligonucleotides, J. Med. Chem., 39, 5100-5109, 1996.
109. Prakash, T. P. et al., Zwitterionic oligonucleotides with 2′-o-[3-(n, n-dimethylamino)propyl]-RNA modification: Synthesis and properties, Tetrahedron Lett., 41, 4855-4859, 2000.
110. Prakash, T. P. et al., 2′-O-[2-(guanidinium)ethyl]-modified oligonucleotides: stabilizing effect on duplex and triplex structures, Org. Lett., 6, 1971-1974, 2004.
111. Prhavc, M. et al., 2′-O-[2-[2-(N, N-dimethylamino)ethoxy]ethyl] modified oligonucleotides:symbiosis of charge interaction factors and stereoelectronic effects, Org. Lett., 5, 2017-2020, 2003.
112. Prakash, T. P. et al., Synthesis of 2′-O-[2-[(N, N-dimethylamino)oxy]ethyl] modified nucleosides and oligonucleotides, J. Org. Chem., 67, 357-369, 2002.
113. Prakash, T. P. et al., 2′-O-[2-[(N, N-dimethylamino)oxy]ethyl]-modified oligonucleotides inhibit expression of mRNA in vitro and in vivo, Nucleic Acids Res., 32, 828-833, 2004.
114. Pattanayek, R. et al., Structural rationalization of a large difference in RNA affinity despite a small difference in chemistry between two 2′-O-modified nucleic acid analogues, J. Am. Chem. Soc., 126, 15,006-15,007, 2004.
115. Prakash, T. P. et al., 2′-O-[2-(Amino)-2-oxoethyl] oligonucleotides, Org. Lett., 5, 403-406, 2003.
116. Lima, W. F. et al., Structural requirements at the catalytic site of the heteroduplex substrate for human RNase H1 catalysis, J. Biol. Chem., 279, 36,317-36,326, 2004.
117. Nielsen, K. D. et al., Oligonucleotide analogues containing 4′-C-(hydroxymethyl)uridine: synthesis, evaluation and mass spectrometric analysis, Bioorg. Med. Chem., 3, 1493-1502, 1995.
118. Fensholdt, J., Thrane, H., and Wengel, J., Synthesis of oligodeoxynucleotides containing 4′-C-(hydroxymethyl)thymidine: novel promising antisense molecules, Tetrahedron Lett., 36, 2535-2538, 1995.
119. Wang, G. et al., Biophysical and biochemical properties of oligodeoxy-nucleotides containing 4′-Cand 5′-C-substituted thymidines, Bioorg. Med. Chem. Lett., 9, 885-890, 1999.
120. Wang, G. and Seifert, W. E., Synthesis and evaluation of oligodeoxynucleotides containing 4′-Csubstituted thymidines, Tetrahedron Lett., 37, 6515-6518, 1996.
121. Pfundheller, H. M. and Wengel, J., Oligonucleotides containing 4′-C-aminomethyl-2′-modified thymidines show increased binding affinity towards DNA and RNA, Bioorg. Med. Chem. Lett., 9, 2667-2672, 1999.
122. Joergensen, P. N., Stein, P. C., and Wengel, J., Synthesis of 3′-C-(hydroxymethyl)thymidine: introduction of a novel class of deoxynucleosides and oligodeoxynucleotides, J. Am. Chem. Soc., 116, 2231-2232, 1994.
123. Svendsen, M. L. et al., Oligodeoxynucleotide analogs containing 3′-deoxy-3′-C-threohydroxymethylthymidine:synthesis, hybridization properties and enzymic stability, Tetrahedron, 49, 11,341-11,352, 1993.
124. Saha, A. K. et al., 5′-Me-DNA-a new oligonucleotide analog: synthesis and biochemical properties, J. Org. Chem., 60, 788-789, 1995.
125. Obika, S. et al., Synthesis of 2′-O,4′-C-methyleneuridine and-cytidine. Novel bicyclic nucleosides having a fixed C3′-endo sugar puckering, Tetrahedron Lett., 38, 8735-8738, 1997.
126. Obika, S. et al., Stability and structural features of the duplexes containing nucleoside analogs with a fixed N-type conformation, 2′-O,4′-C-methyleneribonucleosides, Tetrahedron Lett., 39, 5401-5404, 1998.
127. Koshkin, A. A. et al., LNA (locked nucleic acids): synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerization, and unprecedented nucleic acid recognition, Tetrahedron, 54, 3607-3630, 1998.
128. Singh, S. K. et al., LNA (locked nucleic acids): synthesis and high-affinity nucleic acid recognition, Chem. Commun., 455-456, 1998.
129. Wengel, J., Synthesis of 3′-C-and 4′-C-branched oligodeoxynucleotides and the development of locked nucleic acid (LNA), Acc. Chem. Res., 32, 301-310, 1999.
130. Nielsen, K. E. et al., NMR studies of fully modified locked nucleic acid (LNA) hybrids: solution structure of an LNA:RNA hybrid and characterization of an LNA:DNA hybrid, Bioconjug. Chem., 15, 449-457, 2004.
131. Nielsen, K. E. and Spielmann, H. P., The structure of a mixed LNA/DNA:RNA duplex is driven by conformational coupling between LNA and deoxyribose residues as determined from 13C relaxation measurements, J. Am. Chem. Soc., 127, 15,273-15,282, 2005.
132. Petersen, M. et al., Locked nucleic acid (LNA) recognition of RNA: NMR solution structures of LNA:RNA hybrids, J. Am. Chem. Soc., 124, 5974-5982, 2002.
133. Elmen, J. et al., Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality, Nucleic Acids Res., 33, 439-447, 2005.
134. Braasch, D. A. et al., RNA interference in mammalian cells by chemically-modified RNA, Biochemistry, 42, 7967-7975, 2003.
135. Hornung, V. et al., Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7, Nat. Med., 11, 263-270, 2005.
136. Orom, U. A., Kauppinen, S., and Lund, A. H., LNA-modified oligonucleotides mediate specific inhibition of microRNA function, Gene, 372, 137-141, 2006.
137. Darfeuille, F. et al., LNA/DNA chimeric oligomers mimic RNA aptamers targeted to the TAR RNA element of HIV-1, Nucleic Acids Res., 32, 3101-3107, 2004.
138. Schmidt, K. S. et al., Application of locked nucleic acids to improve aptamer in vivo stability and targeting function, Nucleic Acids Res., 32, 5757-5765, 2004.
139. Jepsen, J. S., Sorensen, M. D., and Wengel, J., Locked nucleic acid: a potent nucleic acid analog in therapeutics and biotechnology, Oligonucleotides, 14, 130-146, 2004.
140. Kurreck, J. et al., Design of antisense oligonucleotides stabilized by locked nucleic acids, Nucleic Acids Res., 30, 1911-1918, 2002.
141. Fluiter, K. et al., On the in vitro and in vivo properties of four locked nucleic acid nucleotides incorporated into an anti-H-Ras antisense oligonucleotide, Chem. Biochem., 6, 1104-1109, 2005.
142. Fluiter, K. et al., In vivo tumor growth inhibition and biodistribution studies of locked nucleic acid (LNA) antisense oligonucleotides, Nucleic Acids Res., 31, 953-962, 2003.
143. Swayze, E. E. et al., Antisense oligonucleotides containing locked nucleic acid (LNA) improve potency and cause significant hepatotoxicity in animals., Nucl. Acids Res., 35, 687-700, 2007.
144. Rajwanshi, V. K. et al., The eight stereoisomers of LNA (locked nucleic acid): a remarkable family of strong RNA binding molecules, Angew. Chem. Int. Ed. Engl., 39, 1656-1659, 2000.
145. Nielsen, K. M. et al., alpha-L-LNA (alpha-L-ribo configured locked nucleic acid) recognition of DNA:an NMR spectroscopic study, Chemistry, 8, 3001-3009, 2002.
146. Nielsen, J. T., Stein, P. C., and Petersen, M., NMR structure of an alpha-L-LNA:RNA hybrid:structural implications for RNase H recognition, Nucleic Acids Res., 31, 5858-5867, 2003.
147. Frieden, M. et al., Expanding the design horizon of antisense oligonucleotides with alpha-l-LNA, Nucleic Acids Res., 31, 6365-6372, 2003.
148. Singh, S. K., Kumar, R., and Wengel, J., Synthesis of novel bicyclo[2.2.1] ribonucleosides: 2′-aminoand 2′-thio-LNA monomeric nucleosides, J. Org. Chem., 63, 6078-6079, 1998.
149. Morita, K. et al., 2′-O,4′-C-ethylene-bridged nucleic acids (ENA): highly nuclease-resistant and thermodynamically stable oligonucleotides for antisense drug, Bioorg. Med. Chem. Lett., 12, 73-76, 2002.
150. Morita, K. et al., Synthesis and properties of 2′-O,4′-C-ethylene-bridged nucleic acids (ENA) as effective antisense oligonucleotides, Bioorg. Med. Chem., 11, 2211-2226, 2003.
151. Morita, K. et al., Inhibition of VEGF mRNA by 2′-O,4′-C-ethylene-bridged nucleic acids (ENA) antisense oligonucleotides and their influence on off-target gene expressions, Nucleos. Nucleot. Nucleic Acids, 25, 503-521, 2006.
152. Horie, M. et al., Comparison between properties of 2′-O,4′-C-ethylene-bridged nucleic acid (ENA) phosphorothioate oligonucleotides and N3′-P5′ thiophosphoramidate oligonucleotides, Nucleos. Nucleot. Nucleic Acids, 25, 231-242, 2006.
153. Hari, Y. et al., Synthesis and properties of 2′-O,4′-C-methyleneoxymethylene bridged nucleic acid, Bioorg. Med. Chem., 14, 1029-1038, 2006.
154. Wang, G. et al., Conformationally locked nucleosides. Synthesis and hybridization properties of oligodeoxynucleotides containing 2′,4′-C-bridged 2′-deoxynucleosides, Bioorg. Med. Chem. Lett., 9, 1147-1150, 1999.
155. Imanishi, T., Obika, S., and Miyashita, K., Nuclease resistant oligonucleotide analogue: 2′-O,4′-C-N-O bridged nucleic acid (2′,4′-BNANC) with efficient duplex and triplex formation, WO 2005021570, 2005.
156. Kvarno, L. and Wengel, J., Novel bicyclic nucleoside analogue (1S,5S,6S)-6-hydroxy-5-hydroxymethyl-1-(uracil-1-yl)-3,8-dioxabicyclo[3.2.1]octane: synthesis and incorporation into oligodeoxynucleotides, J. Org. Chem., 66, 5498-5503, 2001.
157. Pradeepkumar, P. I. et al., Synthesis, physicochemical and biochemical studies of 1′,2′-oxetane constrained adenosine and guanosine modified oligonucleotides, and their comparison with those of the corresponding cytidine and thymidine analogues, J. Am. Chem. Soc., 126, 11,484-11,499, 2004.
158. Opalinska, J. B. et al., Oxetane modified, conformationally constrained, antisense oligodeoxyribonucleotides function efficiently as gene silencing molecules, Nucleic Acids Res., 32, 5791-5799, 2004.
159. Christensen, N. K. et al., A novel class of oligonucleotide analogs containing 2′-O,3′-C-linked [3.2.0]bicycloarabinonucleoside monomers: synthesis, thermal affinity studies, and molecular modeling, J. Am. Chem. Soc., 120, 5458-5463, 1998.
160. Tommerholt, H. V. et al., NMR solution structure of dsDNA containing a bicyclic D-arabino-configured nucleotide fixed in an O4′-endo sugar conformation, Org. Biomol. Chem., 1, 1790-1797, 2003.
161. Sekiguchi, M. et al., Synthesis and properties of a novel bridged nucleic acid analogue, 5′-amino-3′,5′-BNA, Nucleos. Nucleot. Nucleic Acids, 24, 1097-1100, 2005.
162. Bolli, M., Trafelet, H. U., and Leumann, C., Watson-Crick base-pairing properties of bicyclo-DNA, Nucleic Acids Res., 24, 4660-4667, 1996.
163. Renneberg, D. and Leumann, C. J., Watson-Crick base-pairing properties of tricyclo-DNA, J. Am. Chem. Soc., 124, 5993-6002, 2002.
164. Renneberg, D. et al., Antisense properties of tricyclo-DNA, Nucleic Acids Res., 30, 2751-2757, 2002.
165. Ittig, D. et al., Nuclear antisense effects in cyclophilin A pre-mRNA splicing by oligonucleotides: a comparison of tricyclo-DNA with LNA, Nucleic Acids Res., 32, 346-353, 2004.
166. Altmann, K.-H. et al., 1′,6′-Methano carbocyclic thymidine: synthesis, x-ray crystal structure, and effect on nucleic acid duplex stability, Tetrahedron Lett., 35, 7625-7628, 1994.
167. Altmann, K.-H. et al., 4′,6′-Methano carbocyclic thymidine: a conformationally constrained building block for oligonucleotides, Tetrahedron Lett., 35, 2331-2334, 1994.
168. Marquez, V. E. et al., Nucleosides with a twist. Can fixed forms of sugar ring pucker influence biological activity in nucleosides and oligonucleotides?, J. Med. Chem., 39, 3739-3747, 1996.
169. Obika, S. et al., Synthesis and conformation of 3′,4′-BNA monomers, 3′-O,4′-C-methyleneribonucleosides, Tetrahedron, 58, 3039-3049, 2002.
170. Obika, S. et al., Preparation and properties of 2′,5′-linked oligodeoxyribonucleotide analogs containing 3′-O,4′-C-methylene-ribonucleosides, Bioorg. Med. Chem. Lett., 9, 515-518, 1999.
171. Madsen, A. S. et al., Synthesis, nucleic acid hybridization properties and molecular modelling studies of conformationally restricted 3′-O,4′-C-methylene-linked alpha-L-ribonucleotides, Carbohydr. Res., 341, 1398-1407, 2006.
172. Sekiguchi, M. et al., Synthesis and properties of trans-3′,4′-bridged nucleic acids having typical S-type sugar conformation, J. Org. Chem., 71, 1306-1316, 2006.
173. Jones, G. D. et al., Investigation of some properties of oligodeoxynucleotides containing 4′-thio-2′-deoxynucleotides: duplex hybridization and nuclease sensitivity, Nucleic Acids Res., 24, 4117-4122, 1996.
174. Leydier, C. et al., 4′-Thio-RNA: synthesis of mixed base 4′-thio-oligoribonucleotides, nuclease resistance, and base pairing properties with complementary single and double strand, Antisense Res. Dev., 5, 167-174, 1995.
175. Bellon, L. et al., 4′-Thio-oligo-beta-D-ribonucleotides: synthesis of beta-4′-thio-oligouridylates, nuclease resistance, base pairing properties, and interaction with HIV-1 reverse transcriptase, Nucleic Acids Res., 21, 1587-1593, 1993.
176. Haeberli, P. et al., Syntheses of 4′-thioribonucleosides and thermodynamic stability and crystal structure of RNA oligomers with incorporated 4′-thiocytosine, Nucleic Acids Res., 33, 3965-3975, 2005.
177. Hoshika, S. et al., RNA interference induced by siRNAs modified with 4′-thioribonucleosides in cultured mammalian cells, FEBS Lett., 579, 3115-3118, 2005.
178. Dande, P. et al., Improving RNA interference in mammalian cells by 4′-thio-modified small interfering RNA (siRNA): effect on siRNA activity and nuclease stability when used in combination with 2′-O-alkyl modifications, J. Med. Chem., 49, 1624-1634, 2006.
179. Hoshika, S. et al., Investigation of physical and physiological properties of 4′-thioribonucleotide (4′-thioRNA), Nucleic Acids Res. Suppl., 3, 209-210, 2003.
180. Hoshika, S., Minakawa, N., and Matsuda, A., Synthesis and physical and physiological properties of 4′-thioRNA: application to post-modification of RNA aptamer toward NF-kappaB, Nucleic Acids Res., 32, 3815-3825, 2004.
181. Altmann, K.-H., Kesseiring, R., and Pieles, U., 6′-Carbon-substituted carbocyclic analogs of 2′-deoxyribonucleosides-synthesis and effect on DNA/RNA duplex stability, Tetrahedron, 52, 12,699-12,722, 1996.
182. Altmann, K.-H. et al., The evaluation of 2′-and 6′-substituted carbocyclic nucleosides as building blocks for antisense oligodeoxyribonucleotides, Bioorg. Med. Chem. Lett., 5, 431-436, 1995.
183. Altmann, K.-H. et al., Synthesis of an azathymidine and its incorporation in oligonucleotides, Angew. Chem., 106, 1735-1738, 1994.
184. Schoning, K. et al., Chemical etiology of nucleic acid structure: the alpha-threofuranosyl-(3′→2′) oligonucleotide system, Science, 290, 1347-1351, 2000.
185. Pallan, P. S. et al., Why does TNA cross-pair more strongly with RNA than with DNA? An answer from X-ray analysis, Angew. Chem. Int. Ed. Engl., 42, 5893-5895, 2003.
186. Eschenmoser, A., Chemical etiology of nucleic acid structure, Science, 284, 2118-2124, 1999.
187. Egli, M. et al., Crystal structure of homo-DNA and nature’s choice of pentose over hexose in the genetic system, J. Am. Chem. Soc., 128, 10,847-10,856, 2006.
188. Van Aerschot, A., Conformational restriction as a means for obtaining steric blocking antisense oligonucleotides, in Modified Nucleosides: Synthesis and Applications, Loakes, D. ed., Research Signpost, Kerala, India, 2002, pp. 17-32.
189. Herdewijn, P., Conformationally restricted carbohydrate-modified nucleic acids and antisense technology, Biochim. Biophys. Acta, 1489, 167-179, 1999.
190. Vandermeeren, M. et al., Biological activity of hexitol nucleic acids targeted at Ha-ras and intracellular adhesion molecule-1 mRNA, Biochem. Pharmacol., 59, 655-663, 2000.
191. Kang, H. et al., Inhibition of MDR1 gene expression by chimeric HNA antisense oligonucleotides, Nucleic Acids Res., 32, 4411-4419, 2004.
192. Kolb, G. et al., Hexitol nucleic acid-containing aptamers are efficient ligands of HIV-1 TAR RNA, Biochemistry, 44, 2926-2933, 2005.
193. Lescrinier, E. et al., Solution structure of a HNA-RNA hybrid, Chem. Biol., 7, 719-731, 2000.
194. Maier, T. et al., Reinforced HNA backbone hydration in the crystal structure of a decameric HNA/RNA hybrid, J. Am. Chem. Soc., 127, 2937-2943, 2005.
195. Van Aerschot, A. et al., Improved hybridisation potential of oligonucleotides comprising O-methylated anhydrohexitol nucleoside congeners, Nucleic Acids Res., 29, 4187-4194, 2001.
196. Wang, J. et al., Cyclohexene nucleic acids (CeNA): serum stable oligonucleotides that activate RNase H and increase duplex stability with complementary RNA, J. Am. Chem. Soc., 122, 8595-8602, 2000.
197. Nauwelaerts, K. et al., Cyclohexenyl nucleic acids: conformationally flexible oligonucleotides, Nucl. Acids Res., 33, 2452-2463, 2005.
198. Herdewijn, P., Heterocyclic modifications of oligonucleotides and antisense technology, Antisense Nucleic Acid Drug Dev., 10, 297-310, 2000.
199. Revenkar, G. R. and Rao, T. S., DNA with Altered Bases, in Comprehensive Natural Products Chemistry, Barton, D. H. R., Nakanishi, K., and Kool, E. T., eds., Pergamon Press, Oxford, 1999, pp. 313-339.
200. Sanghvi, Y. S. et al., Antisense oligodeoxynucleotides: synthesis, biophysical and biological evaluation of oligodeoxynucleotides containing modified pyrimidines, Nucleic Acids Res., 21, 3197-3203, 1993.
201. Sagi, J. et al., Destabilization of the duplex and the high-salt Z-form of poly(dG-methyl5dC) by substitution of ethyl for the 5-methyl group, Int. J. Biol. Macromol., 13, 329-336, 1991.
202. Henry, S. et al., Chemically modified oligonucleotides exhibit decreased immune stimulation in mice, J. Pharmacol. Exp. Ther., 292, 468-479, 2000.
203. Devoe, H. and Tinoco, I., Jr., The stability of helical polynucleotides: base contributions, J. Mol. Biol., 4, 500-517, 1962.
204. Froehler, Brian C. et al., Oligodeoxynucleotides containing C-5 propyne analogs of 2′-deoxyuridine and 2′-deoxycytidine, Tetrahedron Lett., 33, 5307-5310, 1992.
205. Wagner, R. W. et al., Antisense gene inhibition by oligonucleotides containing C-5 propyne pyrimidines, Science, 260, 1510-1513, 1993.
206. Moulds, C. et al., Site and mechanism of antisense inhibition by C-5 propyne oligonucleotides, Biochemistry, 34, 5044-5053, 1995.
207. Gutierrez, A. J. et al., Antisense gene inhibition by C-5-substituted deoxyuridine-containing oligodeoxynucleotides, Biochemistry, 36, 743-748, 1997.
208. Wagner, R. W. et al., Potent and selective inhibition of gene expression by an antisense heptanucleotide, Nat. Biotechnol., 14, 840-844, 1996.
209. Wagner, R. W., Structure-activity relationships in cell culture, Ciba Found. Symp., 209, 142-154; discussion 154-157, 1997.
210. Shen, L. et al., Evaluation of C-5 propynyl pyrimidine-containing oligonucleotides in vitro and in vivo, Antisense Nucleic Acid Drug Dev., 13, 129-142, 2003.
211. Gutierrez, A. J. et al., 5-Heteroaryl-2′-deoxyuridine analogs. Synthesis and incorporation into highaffinity oligonucleotides, J. Am. Chem. Soc., 116, 5540-5544, 1994.
212. Lin, K.-Y., Jones, R. J., and Matteucci, M., Tricyclic 2′-deoxycytidine analogs: syntheses and incorporation into oligodeoxynucleotides which have enhanced binding to complementary RNA, J. Am. Chem. Soc., 117, 3873-3874, 1995.
213. Flanagan, W. M. et al., Cellular penetration and antisense activity by a phenoxazine-substituted heptanucleotide, Nat. Biotechnol., 17, 48-52, 1999.
214. Lin, K.-Y. and Matteucci, M. D., A cytosine analog capable of clamp-like binding to a guanine in helical nucleic acids, J. Am. Chem. Soc., 120, 8531-8532, 1998.
215. Flanagan, W. M. et al., A cytosine analog that confers enhanced potency to antisense oligonucleotides, Proc. Natl. Acad. Sci. USA., 96, 3513-3518, 1999.
216. Wilds, C. J. et al., Structural basis for recognition of guanosine by a synthetic tricyclic cytosine analogue:Guanidinium G-clamp, Helv. Chim. Acta, 86, 966-978, 2003.
217. Sazani, P., Astriab-Fischer, A., and Kole, R., Effects of base modifications on antisense properties of 2′-O-methoxyethyl and PNA oligonucleotides, Antisense Nucleic Acid Drug Dev., 13, 119-128, 2003.
218. Holmes, S. C. and Gait, M. J., The synthesis of 2′-O-methyl G-clamp containing oligonucleotides and their inhibition of the HIV-1 Tat-TAR interaction, Nucleos. Nucleot. Nucleic Acids, 22, 1259-1262, 2003.
219. Connolly, B. A. and Newman, P. C., Synthesis and properties of oligonucleotides containing 4-thiothymidine, 5-methyl-2-pyrimidinone-1-beta-D(2′-deoxyriboside) and 2-thiothymidine, Nucleic Acids Res., 17, 4957-4974, 1989.
220. Newman, P. C. et al., Incorporation of a complete set of deoxyadenosine and thymidine analogues suitable for the study of protein nucleic acid interactions into oligodeoxynucleotides. Application to the EcoRV restriction endonuclease and modification methylase, Biochemistry, 29, 9891-9901, 1990.
221. Diop-Frimpong, B. et al., Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2′-O-[2-(methoxy)ethyl]-2-thiothymidines, Nucleic Acids Res., 33, 5297-5307, 2005.
222. Howard, F. B. and Miles, H. T., 2NH2A X T helices in the ribo-and deoxypolynucleotide series. Structural and energetic consequences of 2NH2A substitution, Biochemistry, 23, 6723-6732, 1984.
223. Lamm, G. M. et al., Antisense probes containing 2-aminoadenosine allow efficient depletion of U5 snRNP from HeLa splicing extracts, Nucleic Acids Res., 19, 3193-3198, 1991.
224. Gryaznov, S. M. and Schultz, R. G., Stabilization of DNA:DNA and DNA:RNA duplex by substitutionof 2′-deoxyadenosine with 2′-deoxy-2-aminoadenosine, Terahedron Lett., 36, 2489-2492, 1994.
225. Ramasamy, K. S. et al., Remarkable enhancement of binding affinity of heterocycle-modified DNA to DNA and RNA. Synthesis, characterization and biophysical evaluation of N2-imidazolylpropylguanine and N2-imidazolylpropyl-2-aminoadenine modified oligonucleotides, Tetrahedron Lett., 35, 215-218, 1994.
226. Manoharan, M. et al., Oligonucleotides bearing cationic groups: N2-(3-aminopropyl)deoxyguanosine. Synthesis, enhanced binding properties and conjugation chemistry, Tetrahedron Lett., 37, 7675-7678, 1996.
227. Balow, G. et al., Biophysical and antisense properties of oligodeoxynucleotides containing 7-propynyl-, 7-iodo-and 7-cyano-7-deaza-2-amino-2′-deoxyadenosines, Nucleic Acids Res., 26, 3350-3357, 1998.
228. Buhr, C. A. et al., Oligodeoxynucleotides containing C-7 propyne analogs of 7-deaza-2′-deoxyguanosine and 7-deaza-2′-deoxyadenosine, Nucleic Acids Res., 24, 2974-2980, 1996.
229. Manoharan, M., Oligonucleotide conjugates in antisense technology, in Antisense drug technology:Principles, strategies, and applications, Crooke, S. T., ed., Marcel Dekker, New York, 2001, pp. 391-470.
230. Manoharan, M., Oligonucleotide conjugates as potential antisense drugs with improved uptake, biodistribution, targeted delivery, and mechanism of action, Antisense Nucleic Acid Drug Dev., 12, 103-28, 2002.
231. Bijsterbosch, M. K. et al., Delivery of cholesteryl-conjugated phosphorothioate oligodeoxynucleotides to Kupffer cells by lactosylated low-density lipoprotein, Biochem. Pharmacol., 62, 627-633, 2001.
232. Bijsterbosch, M. K. et al., Modulation of plasma protein binding and in vivo liver cell uptake of phosphorothioate oligodeoxynucleotides by cholesterol conjugation, Nucleic Acids Res., 28, 2717-2725, 2000.
233. Bijsterbosch, M. K. et al., bis-Cholesteryl-conjugated phosphorothioate oligodeoxynucleotides are highly selectively taken up by the liver, J. Pharmacol. Exp. Ther., 302, 619-626, 2002.
234. Krutzfeldt, J. et al., Silencing of microRNAs in vivo with “antagomirs,” Nature, 43, 685-689, 2005.
235. Henry, S. P. et al., Toxicological properties of several novel oligonucleotide analogs in mice, Anticancer. Drug Des., 12, 1-14, 1997.
236. Herbert, B.-S. et al., Lipid modification of GRN163, an N3′-P5′ thio-phosphoramidate oligonucleotide, enhances the potency of telomerase inhibition, Oncogene, 24, 5262-5268, 2005.
237. Kastelein, J. J. P. et al., Potent reduction of apolipoprotein B and LDL cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B, Circulation, in press, 2006.
238. Karras, J. G. et al., Peptide nucleic acids are potent modulators of endogenous pre-mRNA splicing of the murine interleukin-5 receptor-a chain, Biochemistry, 40, 7853-7859, 2001.
239. Baker, B. F. et al., 2′-O-(2-Methoxy)ethyl-modified anti-intercellular adhesion molecule 1 (ICAM-1) oligonucleotides selectively increase the ICAM-1 mRNA level and inhibit formation of the ICAM-1 translation initiation complex in human umbilical vein endothelial cells, J. Biol. Chem., 272, 11,994-12,000, 1997.
240. Vickers, T. A. et al., Fully modified 2′ MOE oligonucleotides redirect polyadenylation, Nucleic Acids Res., 29, 1293-1299, 2001.
241. Esau, C. et al., miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting, Cell Metabol., 3, 87-98, 2006.
242. Davis, S. et al., Improved targeting of miRNA with antisense oligonucleotides, Nucl. Acids Res., 34, 2294-2304, 2006.