Lipid conjugated oligonucleotides: A useful strategy for delivery

Bioconjugate Chemistry

Volumn 23, Issue 6, 2012, Pages 1091-1104

  Raouane, Mouna ^a,b   Desmaële, Didier ^a   Urbinati, Giorgia ^b   Massaad Massade, Liliane ^b   Couvreur, Patrick ^a  

^a UNIV PARIS SUD   (France)

^b INSTITUT GUSTAVE ROUSSY   (France)

Author keywords

[No Author keywords available]

Indexed keywords

FATTY ACIDS; NUCLEIC ACIDS;

ANTISENSE OLIGONUCLEOTIDES; CLINICAL APPLICATION; HYDROPHOBIC MOIETIES; NANOPLEXES; NEUTRAL LIPID; OLIGONUCLEOTIDE CONJUGATES; POSITIVELY CHARGED; STRONG INTERACTION; THERAPEUTIC AGENTS; TRANSMEMBRANES;

OLIGONUCLEOTIDES;

ANTISENSE OLIGONUCLEOTIDE; CHOLESTEROL; CHOLIC ACID DERIVATIVE; FATTY ACID; LIPOSOME; NUCLEIC ACID; SINGLE STRANDED DNA; SMALL INTERFERING RNA; SQUALENE;

AMINO TERMINAL SEQUENCE; CARBOXY TERMINAL SEQUENCE; CELL MEMBRANE PERMEABILITY; CELL MIGRATION; CLICK CHEMISTRY; COVALENT BOND; CYTOPLASM; DISULFIDE BOND; DNA SEQUENCE; ENDOCYTOSIS; ENDOSOME; EXTRACELLULAR MATRIX; GENE DELIVERY SYSTEM; HUMAN; HYDROPHOBICITY; IN VIVO GENE TRANSFER; LIPOPHILICITY; NONHUMAN; PHAGOCYTOSIS; REVIEW; RNA INTERFERENCE;

ANIMALS; DRUG CARRIERS; HUMANS; LIPID METABOLISM; LIPIDS; OLIGONUCLEOTIDES; OLIGONUCLEOTIDES, ANTISENSE; RNA, SMALL INTERFERING;

EID: 84862189151     PISSN: 10431802     EISSN: 15204812     Source Type: Journal    
DOI: 10.1021/bc200422w     Document Type: Review

References (124)

1. Crooke, S. T. (1992) Oligonucleotide therapy. Curr. Opin. Biotechnol. 3, 656-661.
2. Da Ros, T., Spalluto, G., Prato, M., Saison-Behmoaras, T., Boutorine, A., and Cacciari, B. (2005) Oligonucleotides and oligonucleotide conjugates: a new approach for cancer treatment. Curr. Med. Chem. 12, 71-88.
3. Opalinska, J. B., and Gewirtz, A. M. (2002) Nucleic-acid therapeutics: basic principles and recent applications. Nat. Rev. Drug Discovery 1, 503-514.
4. Kim, D. H., and Rossi, J. J. (2007) Strategies for silencing human disease using RNA interference. Nat. Rev. Genet. 8, 173-184.
5. Dorsett, Y., and Tuschl, T. (2004) siRNAs: applications in functional genomics and potential as therapeutics. Nat. Rev. Drug Discovery 3, 318-329.
6. Manoharan, M. (2002) Oligonucleotide conjugates as potential antisense drugs with improved uptake, biodistribution, targeted delivery, and mechanism of action. Antisense Nucleic Acid Drug Dev. 12, 103-128.
7. de Fougerolles, A., Vornlocher, H. P., Maraganore, J., and Lieberman, J. (2007) Interfering with disease: a progress report on siRNA-based therapeutics. Nat. Rev. Drug Discovery 6, 443-453.
8. Chan, J. H., Lim, S., and Wong, W. S. (2006) Antisense oligonucleotides: from design to therapeutic application. Clin. Exp. Pharmacol. Physiol. 33, 533-540.
9. Davis, M. E., Zuckerman, J. E., Choi, C. H., Seligson, D., Tolcher, A., Alabi, C. A., Yen, Y., Heidel, J. D., and Ribas, A. (2011) Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464, 1067-1070.
10. Geisbert, T. W., Lee, A. C., Robbins, M., Geisbert, J. B., Honko, A. N., Sood, V., Johnson, J. C., de Jong, S., Tavakoli, I., Judge, A., Hensley, L. E., and Maclachlan, I. (2010) Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study. Lancet 375, 1896-1905.
11. Gondi, C. S., and Rao, J. S. (2009) Concepts in in vivo siRNA delivery for cancer therapy. J. Cell Physiol. 220, 285-291.
12. Halder, J., Kamat, A. A., Landen, C. N. Jr., Han, L. Y., Lutgendorf, S. K., Lin, Y. G., Merritt, W. M., Jennings, N. B., Chavez-Reyes, A., Coleman, R. L., Gershenson, D. M., Schmandt, R., Cole, S. W., Lopez-Berestein, G., and Sood, A. K. (2006) Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy. Clin. Cancer Res. 12, 4916-4924.
13. Soutschek, J., Akinc, A., Bramlage, B., Charisse, K., Constien, R., Donoghue, M., Elbashir, S., Geick, A., Hadwiger, P., Harborth, J., John, M., Kesavan, V., Lavine, G., Pandey, R. K., Racie, T., Rajeev, K. G., Rohl, I., Toudjarska, I., Wang, G., Wuschko, S., Bumcrot, D., Koteliansky, V., Limmer, S., Manoharan, M., and Vornlocher, H. P. (2004) Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432, 173-178.
14. Tanaka, T., Mangala, L. S., Vivas-Mejia, P. E., Nieves-Alicea, R., Mann, A. P., Mora, E., Han, H. D., Shahzad, M. M., Liu, X., Bhavane, R., Gu, J., Fakhoury, J. R., Chiappini, C., Lu, C., Matsuo, K., Godin, B., Stone, R. L., Nick, A. M., Lopez-Berestein, G., Sood, A. K., and Ferrari, M. (2010) Sustained small interfering RNA delivery by mesoporous silicon particles. Cancer Res. 70, 3687-3696.
15. Zimmermann, T. S., Lee, A. C., Akinc, A., Bramlage, B., Bumcrot, D., Fedoruk, M. N., Harborth, J., Heyes, J. A., Jeffs, L. B., John, M., Judge, A. D., Lam, K., McClintock, K., Nechev, L. V., Palmer, L. R., Racie, T., Rohl, I., Seiffert, S., Shanmugam, S., Sood, V., Soutschek, J., Toudjarska, I., Wheat, A. J., Yaworski, E., Zedalis, W., Koteliansky, V., Manoharan, M., Vornlocher, H. P., and MacLachlan, I. (2006) RNAi-mediated gene silencing in non-human primates. Nature 441, 111-114.
16. Al-Brahim, N., and Asa, S. L. (2006) Papillary thyroid carcinoma: an overview. Arch. Pathol. Lab. Med. 130, 1057-1062.
17. Kuo, W. T., Huang, H. Y., and Huang, Y. Y. (2009) Intracellular trafficking, metabolism and toxicity of current gene carriers. Curr. Drug Metab. 10, 885-894.
18. Wolfrum, C., Shi, S., Jayaprakash, K. N., Jayaraman, M., Wang, G., Pandey, R. K., Rajeev, K. G., Nakayama, T., Charrise, K., Ndungo, E. M., Zimmermann, T., Koteliansky, V., Manoharan, M., and Stoffel, M. (2007) Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat. Biotechnol. 25, 1149-1157.
19. Ueno, Y., Kawada, K., Naito, T., Shibata, A., Yoshikawa, K., Kim, H. S., Wataya, Y., and Kitade, Y. (2008) Synthesis and silencing properties of siRNAs possessing lipophilic groups at their 3′-termini. Bioorg. Med. Chem. 16, 7698-7704.
20. de Smidt, P. C., Le Doan, T., de Falco, S., and van Berkel, T. J. (1991) Association of antisense oligonucleotides with lipoproteins prolongs the plasma half-life and modifies the tissue distribution. Nucleic Acids Res. 19, 4695-4700.
21. Gissot, A., Camplo, M., Grinstaff, M. W., and Barthelemy, P. (2008) Nucleoside, nucleotide and oligonucleotide based amphiphiles: a successful marriage of nucleic acids with lipids. Org. Biomol. Chem. 6, 1324-1333.
22. Branch, A. D. (1996) A hitchhiker's guide to antisense and nonantisense biochemical pathways. Hepatology 24, 1517-1529.
23. Akhtar, S., and Agrawal, S. (1997) In vivo studies with antisense oligonucleotides. Trends Pharmacol. Sci. 18, 12-18.
24. Walder, R. Y., and Walder, J. A. (1988) Role of RNase H in hybrid-arrested translation by antisense oligonucleotides. Proc. Natl. Acad. Sci. U. S. A. 85, 5011-5015.
25. Valencia-Sanchez, M. A., Liu, J., Hannon, G. J., and Parker, R. (2006) Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 20, 515-524.
26. Matranga, C., Tomari, Y., Shin, C., Bartel, D. P., and Zamore, P. D. (2005) Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123, 607-620.
27. Leuschner, P. J., Ameres, S. L., Kueng, S., and Martinez, J. (2006) Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep. 7, 314-320.
28. Elbashir, S. M., Lendeckel, W., and Tuschl, T. (2001) RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 15, 188-200.
29. Hannon, G. J. (2002) RNA interference. Nature 418, 244-251.
30. Hammond, S. M. (2005) Dicing and slicing: the core machinery of the RNA interference pathway. FEBS Lett. 579, 5822-5829.
31. Paddison, P. J., and Hannon, G. J. (2002) RNA interference: the new somatic cell genetics? Cancer Cell 2, 17-23.
32. Juliano, R., Bauman, J., Kang, H., and Ming, X. (2009) Biological barriers to therapy with antisense and siRNA oligonucleotides. Mol. Pharm. 6, 686-695.
33. Juliano, R. L., Kang, H., Alam, M. R., Dixit, V., and Fisher, M. (2008) Cellular delivery and biological activity of antisense oligonucleotides conjugated to a targeted protein carrier. Bioconjugate Chem. 19, 2182-2188.
34. Behlke, M. A. (2008) Chemical modification of siRNAs for in vivo use. Oligonucleotides 18, 305-319.
35. Crooke, S. T. (2004) Progress in antisense technology. Annu. Rev. Med. 55, 61-95.
36. Juliano, R. L. (2005) Peptide-oligonucleotide conjugates for the delivery of antisense and siRNA. Curr. Opin. Mol. Ther. 7, 132-136.
37. Jain, R. K. (1999) Transport of molecules, particles, and cells in solid tumors. Annu. Rev. Biomed. Eng. 1, 241-263.
38. Mayor, S., and Pagano, R. E. (2007) Pathways of clathrin-independent endocytosis. Nat. Rev. Mol. Cell Biol. 8, 603-612.
39. Bennett, R. M. (1993) As nature intended? The uptake of DNA and oligonucleotides by eukaryotic cells. Antisense Res. Dev. 3, 235-241.
40. Le Doan, T. (2001) Cell binding and internalisation of oligonucleotides. STP Pharm. Sci. 11, 75-82.
41. Juliano, R. L., Alahari, S., Yoo, H., Kole, R., and Cho, M. (1999) Antisense pharmacodynamics: critical issues in the transport and delivery of antisense oligonucleotides. Pharm. Res. 16, 494-502.
42. Wang, L., Prakash, R. K., Stein, C. A., Koehn, R. K., and Ruffner, D. E. (2003) Progress in the delivery of therapeutic oligonucleotides: organ/cellular distribution and targeted delivery of oligonucleotides in vivo. Antisense Nucleic Acid Drug Dev. 13, 169-189.
43. Gao, K., and Huang, L. (2009) Nonviral methods for siRNA delivery. Mol. Pharm. 6, 651-658.
44. Wu, S. Y., and McMillan, N. A. (2009) Lipidic systems for in vivo siRNA delivery. AAPS J. 11, 639-652.
45. Frank-Kamenetsky, M., Grefhorst, A., Anderson, N. N., Racie, T. S., Bramlage, B., Akinc, A., Butler, D., Charisse, K., Dorkin, R., Fan, Y., Gamba-Vitalo, C., Hadwiger, P., Jayaraman, M., John, M., Jayaprakash, K. N., Maier, M., Nechev, L., Rajeev, K. G., Read, T., Rohl, I., Soutschek, J., Tan, P., Wong, J., Wang, G., Zimmermann, T., de Fougerolles, A., Vornlocher, H. P., Langer, R., Anderson, D. G., Manoharan, M., Koteliansky, V., Horton, J. D., and Fitzgerald, K. (2008) Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc. Natl. Acad. Sci. U. S. A. 105, 11915-11920.
46. Xu, L., and Anchordoquy, T. (2011) Drug delivery trends in clinical trials and translational medicine: challenges and opportunities in the delivery of nucleic acid-based therapeutics. J. Pharm. Sci. 100, 38-52.
47. Gao, Y., Liu, X. L., and Li, X. R. (2011) Research progress on siRNA delivery with nonviral carriers. Int. J. Nanomed. 6, 1017-1025.
48. Filion, M. C., and Phillips, N. C. (1997) Toxicity and immunomodulatory activity of liposomal vectors formulated with cationic lipids toward immune effector cells. Biochim. Biophys. Acta 1329, 345-356.
49. Ozpolat, B., Sood, A. K., and Lopez-Berestein, G. (2009) Nanomedicine based approaches for the delivery of siRNA in cancer. J. Intern. Med. 267, 44-53.
50. Mendonca, L. S., Moreira, J. N., de Lima, M. C., and Simoes, S. (2010) Co-encapsulation of anti-BCR-ABL siRNA and imatinib mesylate in transferrin receptor-targeted sterically stabilized liposomes for chronic myeloid leukemia treatment. Biotechnol. Bioeng. 107, 884-893.
51. Mendonca, M., Tanji, M. M., Silva, L. C., Silveira, G. G., Oliveira, S. C., Duarte, A. J., and Benard, G. (2007) Deficient in vitro anti-mycobacterial immunity despite successful long-term highly active antiretroviral therapy in HIV-infected patients with past history of tuberculosis infection or disease. Clin. Immunol. 125, 60-66.
52. Vrignaud, S., Benoit, J. P., and Saulnier, P. (2011) Strategies for the nanoencapsulation of hydrophilic molecules in polymer-based nanoparticles. Biomaterials 32, 8593-8604.
53. Grijalvo, S., Ocampo, S. M., Perales, J. C., and Eritja, R. (2010) Synthesis of oligonucleotides carrying amino lipid groups at the 3′-end for RNA interference studies. J. Org. Chem. 75, 6806-6813.
54. Grijalvo, S., Ocampo, S. M., Perales, J. C., and Eritja, R. (2011) Synthesis of lipid-oligonucleotide conjugates for RNA interference studies. Chem. Biodivers. 8, 287-299.
55. Tolia, N. H., and Joshua-Tor, L. (2007) Slicer and the argonautes. Nat. Chem. Biol. 3, 36-43.
56. Parker, J. S., Roe, S. M., and Barford, D. (2005) Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex. Nature 434, 663-666.
57. Ma, J. B., Yuan, Y. R., Meister, G., Pei, Y., Tuschl, T., and Patel, D. J. (2005) Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature 434, 666-670.
58. Nykanen, A., Haley, B., and Zamore, P. D. (2001) ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell 107, 309-321.
59. Schwarz, D. S., Hutvagner, G., Haley, B., and Zamore, P. D. (2002) Evidence that siRNAs function as guides, not primers, in the Drosophila and human RNAi pathways. Mol. Cell 10, 537-548.
60. Cazorla, S. I., Becker, P. D., Frank, F. M., Ebensen, T., Sartori, M. J., Corral, R. S., Malchiodi, E. L., and Guzman, C. A. (2008) Oral vaccination with Salmonella enterica as a Cruzipain-DNA delivery system confers protective immunity against Trypanosoma cruzi. Infect. Immun. 76, 324-333.
61. Chiu, Y. L., and Rana, T. M. (2003) siRNA function in RNAi: a chemical modification analysis. RNA 9, 1034-1048.
62. Khvorova, A., Reynolds, A., and Jayasena, S. D. (2003) Functional siRNAs and miRNAs exhibit strand bias. Cell 115, 209-216.
63. Schwarz, D. S., Hutvagner, G., Du, T., Xu, Z., Aronin, N., and Zamore, P. D. (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell 115, 199-208.
64. Krieg, A. M., and Stein, C. A. (1995) Phosphorothioate oligodeoxynucleotides: antisense or anti-protein? Antisense Res. Dev. 5, 241.
65. Amarzguioui, M., Holen, T., Babaie, E., and Prydz, H. (2003) Tolerance for mutations and chemical modifications in a siRNA. Nucleic Acids Res. 31, 589-595.
66. Braasch, D. A., Jensen, S., Liu, Y., Kaur, K., Arar, K., White, M. A., and Corey, D. R. (2003) RNA interference in mammalian cells by chemically-modified RNA. Biochemistry 42, 7967-7975.
67. Li, Z. Y., Mao, H., Kallick, D. A., and Gorenstein, D. G. (2005) The effects of thiophosphate substitutions on native siRNA gene silencing. Biochem. Biophys. Res. Commun. 329, 1026-1030.
68. Choung, S., Kim, Y. J., Kim, S., Park, H. O., and Choi, Y. C. (2006) Chemical modification of siRNAs to improve serum stability without loss of efficacy. Biochem. Biophys. Res. Commun. 342, 919-927.
69. Hall, A. H., Wan, J., Shaughnessy, E. E., Ramsay Shaw, B., and Alexander, K. A. (2004) RNA interference using boranophosphate siRNAs: structure-activity relationships. Nucleic Acids Res. 32, 5991-6000.
70. Hall, A. H., Wan, J., Spesock, A., Sergueeva, Z., Shaw, B. R., and Alexander, K. A. (2006) High potency silencing by single-stranded boranophosphate siRNA. Nucleic Acids Res. 34, 2773-2781.
71. Froehler, B., Ng, P., and Matteucci, M. (1988) Phosphoramidate analogues of DNA: synthesis and thermal stability of heteroduplexes. Nucleic Acids Res. 16, 4831-4839.
72. Iwase, R., Toyama, T., and Nishimori, K. (2007) Solid-phase synthesis of modified RNAs containing amide-linked oligoribonucleosides at their 3′-end and their application to siRNA. Nucleosides Nucleotides Nucleic Acids 26, 1451-1454.
73. Prakash, T. P., Allerson, C. R., Dande, P., Vickers, T. A., Sioufi, N., Jarres, R., Baker, B. F., Swayze, E. E., Griffey, R. H., and Bhat, B. (2005) Positional effect of chemical modifications on short interference RNA activity in mammalian cells. J. Med. Chem. 48, 4247-4253.
74. Prakash, T. P., Kraynack, B., Baker, B. F., Swayze, E. E., and Bhat, B. (2006) RNA interference by 2′,5′-linked nucleic acid duplexes in mammalian cells. Bioorg. Med. Chem. Lett. 16, 3238-3240.
75. Alvarez, K., Vasseur, J. J., Beltran, T., and Imbach, J. L. (1999) Photocleavable protecting groups as nucleobase protections allowed the solid-phase synthesis of base-sensitive SATE-prooligonucleotides. J. Org. Chem. 64, 6319-6328.
76. Spinelli, N., Meyer, A., Hayakawa, Y., Imbach, J. L., and Vasseur, J. J. (2002) Use of allylic protecting groups for the synthesis of base-sensitive prooligonucleotides. Eur. J. Org. Chem., 49-56.
77. Czauderna, F., Fechtner, M., Dames, S., Aygun, H., Klippel, A., Pronk, G. J., Giese, K., and Kaufmann, J. (2003) Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells. Nucleic Acids Res. 31, 2705-2716.
78. Kraynack, B. A., and Baker, B. F. (2006) Small interfering RNAs containing full 2′-O-methylribonucleotide-modified sense strands display Argonaute2/eIF2C2-dependent activity. RNA 12, 163-176.
79. Vester, B., and Wengel, J. (2004) LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA. Biochemistry 43, 13233-13241.
80. Wahlestedt, C., Salmi, P., Good, L., Kela, J., Johnsson, T., Hokfelt, T., Broberger, C., Porreca, F., Lai, J., Ren, K., Ossipov, M., Koshkin, A., Jakobsen, N., Skouv, J., Oerum, H., Jacobsen, M. H., and Wengel, J. (2000) Potent and nontoxic antisense oligonucleotides containing locked nucleic acids. Proc. Natl. Acad. Sci. U. S. A. 97, 5633-5638.
81. Grunweller, A., Wyszko, E., Bieber, B., Jahnel, R., Erdmann, V. A., and Kurreck, J. (2003) Comparison of different antisense strategies in mammalian cells using locked nucleic acids, 2′-O-methyl RNA, phosphorothioates and small interfering RNA. Nucleic Acids Res. 31, 3185-3193.
82. Hanvey, J. C., Peffer, N. J., Bisi, J. E., Thomson, S. A., Cadilla, R., Josey, J. A., Ricca, D. J., Hassman, C. F., Bonham, M. A., Au, K. G., et al. (1992) Antisense and antigene properties of peptide nucleic acids. Science 258, 1481-1485.
83. Summerton, J. (1999) Morpholino antisense oligomers: the case for an RNase H-independent structural type. Biochim. Biophys. Acta 1489, 141-158.
84. Summerton, J., and Weller, D. (1997) Morpholino antisense oligomers: design, preparation, and properties. Antisense Nucleic Acid Drug Dev. 7, 187-195.
85. Raouane, M., Desmaele, D., Gilbert-Sirieix, M., Gueutin, C., Zouhiri, F., Bourgaux, C., Lepeltier, E., Gref, R., Ben Salah, R., Clayman, G., Massaad-Massade, L., and Couvreur, P. (2010) Synthesis, characterization, and in vivo delivery of siRNA-squalene nanoparticles targeting fusion oncogene in papillary thyroid carcinoma. J. Med. Chem. 54, 4067-4076.
86. Nishina, K., Unno, T., Uno, Y., Kubodera, T., Kanouchi, T., Mizusawa, H., and Yokota, T. (2008) Efficient in vivo delivery of siRNA to the liver by conjugation of alpha-tocopherol. Mol. Ther. 16, 734-740.
87. Letsinger, R. L., Zhang, G. R., Sun, D. K., Ikeuchi, T., and Sarin, P. S. (1989) Cholesteryl-conjugated oligonucleotides: synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture. Proc. Natl. Acad. Sci. U. S. A. 86, 6553-6556.
88. Moschos, S. A., Jones, S. W., Perry, M. M., Williams, A. E., Erjefalt, J. S., Turner, J. J., Barnes, P. J., Sproat, B. S., Gait, M. J., and Lindsay, M. A. (2007) Lung delivery studies using siRNA conjugated to TAT(48-60) and penetratin reveal peptide induced reduction in gene expression and induction of innate immunity. Bioconjugate Chem. 18, 1450-1459.
89. Godeau, G., Staedel, C., and Barthelemy, P. (2008) Lipid-conjugated oligonucleotides via "click chemistry" efficiently inhibit hepatitis C virus translation. J. Med. Chem. 51, 4374-4376.
90. Chaloin, L., Vidal, P., Lory, P., Mery, J., Lautredou, N., Divita, G., and Heitz, F. (1998) Design of carrier peptide-oligonucleotide conjugates with rapid membrane translocation and nuclear localization properties. Biochem. Biophys. Res. Commun. 243, 601-608.
91. Bongartz, J. P., Aubertin, A. M., Milhaud, P. G., and Lebleu, B. (1994) Improved biological activity of antisense oligonucleotides conjugated to a fusogenic peptide. Nucleic Acids Res. 22, 4681-4688.
92. Tuschl, T. (2002) Expanding small RNA interference. Nat. Biotechnol. 20, 446-448.
93. MacKellar, C., Graham, D., Will, D. W., Burgess, S., and Brown, T. (1992) Synthesis and physical properties of anti-HIV antisense oligonucleotides bearing terminal lipophilic groups. Nucleic Acids Res. 20, 3411-3417.
94. Manoharan, M., Tivel, K. L., and Cook, P. D. (1995) Lipidic Nucleic-Acids. Tetrahedron Lett. 36, 3651-3654.
95. Stetsenko, D. A., and Gait, M. J. (2001) A convenient solidphase method for synthesis of 3′-conjugates of oligonucleotides. Bioconjugate Chem. 12, 576-586.
96. Marasco, C. J., Angelino, N. J., Paul, B., and Dolnick, B. J. (1994) A simplified synthesis of acridine and/or lipid containing oligodeoxynucleotides. Tetrahedron Lett. 35, 3029-3032.
97. Habus, I., Zhao, Q., and Agrawal, S. (1995) Synthesis, hybridization properties, nuclease stability, and cellular uptake of the oligonucleotide - amino-beta-cyclodextrins and adamantane conjugates. Bioconjugate Chem. 6, 327-331.
98. Rait, A., Pirollo, K., Will, D. W., Peyman, A., Rait, V., Uhlmann, E., and Chang, E. H. (2000) 3′-End conjugates of minimally phosphorothioate-protected oligonucleotides with 1-O-hexadecylglycerol: synthesis and anti-ras activity in radiation-resistant cells. Bioconjugate Chem. 11, 153-160.
99. Reed, M. W., Adams, A. D., Nelson, J. S., and Meyer, R. B. Jr. (1991) Acridine- and cholesterol-derivatized solid supports for improved synthesis of 3′-modified oligonucleotides. Bioconjugate Chem. 2, 217-225.
100. Vu, H., Hill, T. S., and Jayaraman, K. (1994) Synthesis and properties of cholesteryl-modified triple-helix forming oligonucleotides containing a triglycyl linker. Bioconjugate Chem. 5, 666-668.
101. Vu, H., Singh, P., Joyce, N., Hogan, M. E., and Jayaraman, K. (1993) Synthesis of cholesteryl supports and phosphoramidites containing a novel peptidyl linker for automated synthesis of triple-helix forming oligonucleotides (TFOs). Nucleic Acids Symp. Ser., 19-20.
102. Will, D. W., and Brown, T. (1992) Attachment of vitamin-E derivatives to oligonucleotides during solid-phase synthesis. Tetrahedron Lett. 33, 2729-2732.
103. Reed, M. W., Lukhtanov, E. A., Gorn, V. V., Lucas, D. D., Zhou, J. H., Pai, S. B., Cheng, Y. C., and Meyer, R. B. Jr. (1995) Structure-activity relationships of cytotoxic cholesterol-modified DNA duplexes. J. Med. Chem. 38, 4587-4596.
104. Matysiak, S., Frank, R., and Pfleiderer, W. (1997) Acetal oligonucleotide conjugates in antisense strategy. Nucleosides Nucleotides 16, 855-861.
105. D'Onofrio, J., Montesarchio, D., De Napoli, L., and Di Fabio, G. (2005) An efficient and versatile solid-phase synthesis of 5′- and 3′-conjugated oligonucleotides. Org. Lett. 7, 4927-4930.
106. Ueno, Y., Inoue, T., Yoshida, M., Yoshikawa, K., Shibata, A., Kitamura, Y., and Kitade, Y. (2008) Synthesis of nuclease-resistant siRNAs possessing benzene-phosphate backbones in their 3′-overhang regions. Bioorg. Med. Chem. Lett. 18, 5194-5196.
107. Lorenz, C., Hadwiger, P., John, M., Vornlocher, H. P., and Unverzagt, C. (2004) Steroid and lipid conjugates of siRNAs to enhance cellular uptake and gene silencing in liver cells. Bioorg. Med. Chem. Lett. 14, 4975-4977.
108. Cheng, K., Ye, Z., Guntaka, R. V., and Mahato, R. I. (2006) Enhanced hepatic uptake and bioactivity of type alpha1(I) collagen gene promoter-specific triplex-forming oligonucleotides after conjugation with cholesterol. J. Pharmacol. Exp. Ther. 317, 797-805.
109. DiFiglia, M., Sena-Esteves, M., Chase, K., Sapp, E., Pfister, E., Sass, M., Yoder, J., Reeves, P., Pandey, R. K., Rajeev, K. G., Manoharan, M., Sah, D. W., Zamore, P. D., and Aronin, N. (2007) Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc. Natl. Acad. Sci. U. S. A. 104, 17204-17209.
110. Lehmann, T. J., and Engels, J. W. (2001) Synthesis and properties of bile acid phosphoramidites 5′-tethered to antisense oligodeoxynucleotides against HCV. Bioorg. Med. Chem. 9, 1827-1835.
111. Polushin, N. N., and Cohen, J. S. (1994) Antisense pro-drugs: 5′-ester oligodeoxynucleotides. Nucleic Acids Res. 22, 5492-5496.
112. Krieg, A. M., Tonkinson, J., Matson, S., Zhao, Q., Saxon, M., Zhang, L. M., Bhanja, U., Yakubov, L., and Stein, C. A. (1993) Modification of antisense phosphodiester oligodeoxynucleotides by a 5′ cholesteryl moiety increases cellular association and improves efficacy. Proc. Natl. Acad. Sci. U. S. A. 90, 1048-1052.
113. Gramlich, P. M., Wirges, C. T., Manetto, A., and Carell, T. (2008) Postsynthetic DNA modification through the copper-catalyzed azide-alkyne cycloaddition reaction. Angew. Chem., Int. Ed. Engl. 47, 8350-8358.
114. Krutzfeldt, J., Rajewsky, N., Braich, R., Rajeev, K. G., Tuschl, T., Manoharan, M., and Stoffel, M. (2005) Silencing of microRNAs in vivo with 'antagomirs'. Nature 438, 685-689.
115. Guzaev, A., and Manoharan, M. (1998) Conjugation of oligonucleotides via an electrophilic tether: N-chloroacetamidohexyl phosphoramidite reagent. Bioorg. Med. Chem. Lett. 8, 3671-3676.
116. Kobylanska, A., Okruszek, A., Stec, and J., W. (1998) Application of oxathiaphospholane method for the synthesis of oligodeoxyribonucleotide 5′-O-conjugates. Nucleosides Nucleotides 17, 1977-1982.
117. Durand, A., and Brown, T. (2007) Synthesis and properties of oligonucleotides containing a cholesterol thymidine monomer. Nucleosides Nucleotides Nucleic Acids 26, 785-794.
118. Kurz, A., Bunge, A., Windeck, A. K., Rost, M., Flasche, W., Arbuzova, A., Strohbach, D., Muller, S., Liebscher, J., Huster, D., and Herrmann, A. (2006) Lipid-anchored oligonucleotides for stable double-helix formation in distinct membrane domains. Angew. Chem., Int. Ed. Engl. 45, 4440-4444.
119. Bryld, T., and Lomholt, C. (2007) Attachment of cholesterol to amino-LNA: synthesis and hybridization properties. Nucleosides Nucleotides Nucleic Acids 26, 1645-1647.
120. Guzaev, A., and Lonnberg, H. (1999) Solid support synthesis of ester linked hydrophobic conjugates of oligonucleotides. Tetrahedron 55, 9101-9116.
121. Kwak, M., and Herrmann, A. (2011) Nucleic acid amphiphiles: synthesis and self-assembled nanostructures. Chem. Soc. Rev. 40, 5745-5755.
122. Patwa, A., Gissot, A., Bestel, I., and Barthelemy, P. (2011) Hybrid lipid oligonucleotide conjugates: synthesis, self-assemblies and biomedical applications. Chem. Soc. Rev. 40, 5844-5854.
123. Wu, Y., Sefah, K., Liu, H., Wang, R., and Tan, W. (2010) DNA aptamer-micelle as an efficient detection/delivery vehicle toward cancer cells. Proc. Natl. Acad. Sci. U. S. A. 107, 5-10.
124. Barthelemy, P., Prata, C. A., Filocamo, S. F., Immoos, C. E., Maynor, B. W., Hashmi, S. A., Lee, S. J., and Grinstaff, M. W. (2005) Supramolecular assemblies of DNA with neutral nucleoside amphiphiles. Chem. Commun. (Camb.), 1261-1263.