DNA/RNA heteroduplex oligonucleotide for highly efficient gene silencing

Nature Communications

Volumn 6, Issue , 2015, Pages

  Nishina, Kazutaka ^a,b   Piao, Wenying ^a,b   Yoshida Tanaka, Kie ^a,b   Sujino, Yumiko ^a,b   Nishina, Tomoko ^a,b   Yamamoto, Tsuyoshi ^c   Nitta, Keiko ^a   Yoshioka, Kotaro ^a,b   Kuwahara, Hiroya ^a,b   Yasuhara, Hidenori ^c   Baba, Takeshi ^c   Ono, Fumiko ^d   Miyata, Kanjiro ^e   Miyake, Koichi ^f   Seth, Punit P ^g   Low, Audrey ^g   Yoshida, Masayuki ^a   Bennett, C Frank ^g   Kataoka, Kazunori ^e,h   Mizusawa, Hidehiro ^a   Obika, Satoshi ^b,c   Yokota, Takanori ^a,b   more..

^a TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^c OSAKA UNIVERSITY   (Japan)

^d The Corporation for Production and Research of Laboratory Primates   (Japan)

^e UNIVERSITY OF TOKYO   (Japan)

^f NIPPON MEDICAL SCHOOL   (Japan)

^g ISIS PHARMACEUTICALS   (United States)

^h UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALINE PHOSPHATASE; ALPHA TOCOPHEROL; ALPHA TOCOPHEROL CONJUGATED COMPLEMENTARY RNA; ANTISENSE OLIGONUCLEOTIDE; CHOLESTEROL; COMPLEMENTARY RNA; DOUBLE STRANDED RNA; GAMMA INTERFERON; HETERODUPLEX; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MESSENGER RNA; RNA OLIGONUCLEOTIDE; SINGLE STRANDED DNA; SMALL INTERFERING RNA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; APOLIPOPROTEIN B; FAT INTAKE; OLIGONUCLEOTIDE;

DNA; DRUG; GENE EXPRESSION; MOLECULAR ANALYSIS; PHENOTYPE; RNA;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHEMICAL STRUCTURE; CONTROLLED STUDY; DRUG EFFICACY; GENE EXPRESSION; GENE SILENCING; LIVER DYSFUNCTION; MALE; MOUSE; NONHUMAN; PHENOTYPE; SINGLE PARENT; ADMINISTRATION AND DOSAGE; ADVERSE EFFECTS; ANIMAL; C57BL MOUSE; CHEMICALLY INDUCED; CHEMISTRY; FAT INTAKE; GENETICS; HUMAN; HYPERCHOLESTEROLEMIA; KNOCKOUT MOUSE; MACACA FASCICULARIS; METABOLISM; NUCLEOTIDE SEQUENCE; PHYSIOLOGY; TRANSGENIC MOUSE;

ALPHA-TOCOPHEROL; ANIMALS; APOLIPOPROTEINS B; BASE SEQUENCE; DIETARY FATS; GENE SILENCING; HUMANS; HYPERCHOLESTEROLEMIA; MACACA FASCICULARIS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; NUCLEIC ACID HETERODUPLEXES; OLIGONUCLEOTIDES; RNA, MESSENGER;

EID: 84938917501     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms8969     Document Type: Article

References (62)

1. Kole, R., Krainer, A. R. and Altman, S. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nat. Rev. Drug Discov. 11, 125-140 (2012
2. Jiang, K. Biotech comes to its antisenses after hard-won drug approval. Nat. Med. 19, 252 (2013
3. Miller, T. M. et al. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol. 12, 435-442 (2013
4. Fitzgerald, K. et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. Lancet 383, 60-68 (2014
5. Coelho, T. et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N. Engl. J. Med. 369, 819-829 (2013
6. Crooke, S. T. and Geary, R. S. Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B. Br. J. Clin. Pharmacol. 76, 269-276 (2013
7. Geary, R. S., Baker, B. F. and Crooke, S. T. Clinical and preclinical pharmacokinetics and pharmacodynamics of mipomersen (kynamro(s)): a second-generation antisense oligonucleotide inhibitor of apolipoprotein B. Clin. Pharmacokinet. 54, 133-146 (2015
8. Gilleron, J. et al. Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat. Biotechnol. 28, 638-646 (2013
9. Haussecker, D. Current issues of RNAi therapeutics delivery and development. J. Control. Release 195, 49-54 (2014
10. Yin, H. et al. Non-viral vectors for gene-based therapy. Nat. Rev. Genet. 15, 541-555 (2014
11. Nair, J. K. et al. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J. Am. Chem. Soc. 136, 16958-16961 (2014
12. Kanasty, R., Dorkin, J. R., Vegas, A. and Anderson, D. Delivery materials for siRNA therapeutics. Nat. Mater. 12, 967-977 (2013
13. Ozcan, G., Ozpolat, B., Coleman, R. L., Sood, A. K. and Lopez-Berestein, G. Preclinical and clinical development of siRNA-based therapeutics. Adv. Drug Deliv. Rev 87, 108-119 (2015
14. Bennett, C. F. and Swayze, E. E. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol. 50, 259-293 (2010
15. Wu, H. et al. Determination of the role of the human RNase H1 in the pharmacology of DNA-like antisense drugs. J. Biol. Chem. 279, 17181-17189 (2004
16. Obika, S. et al. Synthesis of 20-O,40-C-methyleneuridine and -cytidine. Novel bicyclic nucleosides having a fixed C3, -endo sugar puckering. Tetrahedron Lett. 38, 8735-8738 (1997
17. Obika, S. et al. Stability and structural features of the duplexes containing nucleoside analogues with a fixed N-type conformation, 20-O,40-Cmethyleneribonucleosides. Tetrahedron Lett. 39, 5401-5404 (1998
18. Singh, S. K., Koshkin, A. A., Wengel, J. and Nielsen, P. LNA (locked nucleic acids): synthesis and high-affinity nucleic acid recognition. Chem. Commun. 4, 455-456 (1998
19. 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
20. Teplova, M. et al. Crystal structure and improved antisense properties of 2-O-(2-methoxyethyl)-RNA. Nat. Struct. Biol. 6, 535-539 (1999
21. Seth, P. P. et al. Synthesis and biophysical evaluation of 20,40-constrained 20-methoxyethyl and 20,40-constrained 20O-ethyl nucleic acid. J. Org. Chem. 75, 1569-1581 (2010
22. Murray, S. et al. TricycloDNA-modified oligo-2-deoxyribonucleotides reduce scavenger receptor B1 mRNA in hepatic and extra-hepatic tissues-a comparative study of oligonucleotide length, design and chemistry. Nucleic Acids Res. 40, 6135-6143 (2012
23. Straarup, E. M. et al. Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates. Nucleic Acids Res. 38, 7100-7111 (2010
24. Juliano, R. L., Ming, X. and Nakagawa, O. Cellular uptake and intracellular trafficking of antisense and siRNA oligonucleotides. Bioconjug. Chem. 23, 147-157 (2012
25. Nishina, K. et al. Efficient in vivo delivery of siRNA to the liver by conjugation of a-tocopherol. Mol. Ther. 16, 734-740 (2008
26. Uno, Y. et al. High-density lipoprotein facilitates in vivo delivery of a-tocopherol-conjugated short-interfering RNA to the brain. Hum. Gene Ther. 22, 711-719 (2011
27. Nishina, T. et al. Chimeric antisense oligonucleotide conjugated to a-tocopherol. Mol. Ther. Nucleic Acids 4, e220 (2015
28. Birmingham, A. et al. 30 UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat. Methods 3, 199-204 (2006
29. Prakash, T. P. et al. Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice. Nucleic. Acids. Res. 42, 8796-8807 (2014
30. Rigotti, A. Absorption, transport, and tissue delivery of vitamin E. Mol. Aspects Med. 5-6, 423-436 (2007
31. Nowotny, M. et al. Structure of human RNase H1 complexed with an RNA/DNA hybrid: insight into HIV reverse transcription. Mol. Cell 28, 264-276 (2007
32. Tadokoro, T., Chon, H., Koga, Y., Takano, K. and Kanaya, S. Identification of the gene encoding a type 1 RNase H with an N-terminal double-stranded RNA binding domain from a psychrotrophic bacterium. FEBS J. 274, 3715-3727 (2007
33. Lima, W. F. et al. Human RNase H1 discriminates between subtle variations in the structure of the heteroduplex substrate. Mol. Pharmacol. 71, 83-91 (2007
34. Laxton, C. et al. Selection, optimization, and pharmacokinetic properties of a novel, potent antiviral locked nucleic acid-based antisense oligomer targeting hepatitis C virus internal ribosome entry site. Antimicrob. Agents Chemother. 55, 3105-3114 (2011
35. Soutschek, J. et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432, 173-178 (2004
36. Wolfrum, C. et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat. Biotechnol. 25, 1149-1157 (2007
37. Lorenz, C. et al. Steroid and lipid conjugates of siRNAs to enhance cellular uptake and gene silencing in liver cells. Bioorg. Med. Chem. Lett. 14, 4975-4977 (2004
38. Chen, Q. et al. Lipophilic siRNAs mediate efficient gene silencing in oligodendrocytes with direct CNS delivery. J. Control. Release 144, 227-232 (2010
39. Patwa, A., Gissot, A., Bestel, I. and Barthelemy, P. Hybrid lipid oligonucleotide conjugates: synthesis, self-assemblies and biomedical applications. Chem. Soc. Rev. 40, 5844-5854 (2011
40. Haud, N. et al. rnaset2 mutant zebrafish model familial cystic leukoencephalopathy and reveal a role for RNase T2 in degrading ribosomal RNA. Proc. Natl Acad. Sci. USA 108, 1099-1103 (2011
41. Raouane, M., Desmaele, D., Urbinati, G., Massaad-Massade, L. and Couvreur, P. Lipid conjugated oligonucleotides: a useful strategy for delivery. Bioconjug. Chem. 23, 1091-1104 (2012
42. Whitehead, K. A. et al. Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity. Nat. Commun. 5, 4277 (2014
43. Semple, S. C. et al. Rational design of cationic lipids for siRNA delivery. Nat. Biotechnol. 28, 172-176 (2010
44. Akinc, A. et al. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol. Ther. 18, 1357-1364 (2010
45. Prakash, T. P. et al. Lipid nanoparticles improve activity of single-stranded siRNA and gapmer antisense oligonucleotides in animals. ACS Chem. Biol. 8, 1402-1406 (2014
46. Yokota, T. et al. Efficient regulation of viral replication by siRNA in a nonhuman primate surrogate model for hepatitis C. Biochem. Biophys. Res. Commun. 361, 294-300 (2007
47. Kumar, V. et al. Shielding of lipid nanoparticles for siRNA delivery: Impact on physicochemical properties, cytokine induction, and efficacy. Mol. Ther. Nucleic Acids 3, e210 (2014
48. Yu, R. Z. et al. Cross-species comparison of in vivo PK/PD relationships for second-generation antisense oligonucleotides targeting apolipoprotein B-100. Biochem. Pharmacol. 77, 910-919 (2009
49. Koller, E. et al. Mechanisms of single-stranded phosphorothioate modified antisense oligonucleotide accumulation in hepatocytes. Nucleic Acids Res. 39, 4795-4807 (2011
50. Stein, C. A. et al. Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents. Nucleic Acids Res. 38, e3 (2010
51. Swayze, E. E. et al. Antisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals. Nucleic Acids Res. 35, 687-700 (2007
52. Senn, J. J., Burel, S. and Henry, S. P. Non-CpG-containing antisense 2-methoxyethyl oligonucleotides activate a proinflammatory response independent of Toll-like receptor 9 or myeloid differentiation factor 88. J. Pharmacol. Exp. Ther. 314, 972-979 (2005
53. Burel, S. A. et al. Unique O-methoxyethyl ribose-DNA chimeric oligonucleotide induces an atypical melanoma differentiation-associated gene 5-dependent induction of type I interferon response. J. Pharmacol. Exp. Ther. 342, 150-162 (2012
54. Seth, P. P. et al. Structure activity relationships of a-L-LNA modified phosphorothioate gapmer antisense oligonucleotides in animals. Mol. Ther. Nucleic Acids 1, e47 (2012
55. Burel, S. A. et al. Preclinical evaluation of the toxicological effects of a novel constrained ethyl modified antisense compound targeting signal transducer and activator of transcription 3 in mice and cynomolgus monkeys. Nucleic Acids Ther. 23, 213-227 (2013
56. Burdick, A. D. et al. Sequence motifs associated with hepatotoxicity of locked nucleic acid-modified antisense oligonucleotides. Nucleic Acids Res. 42, 4882-4891 (2014
57. Kakiuchi-Kiyota, S. et al. Comparison of hepatic transcription profiles of locked ribonucleic acid antisense oligonucleotides: evidence of distinct pathways contributing to non-target mediated toxicity in mice. Toxicol. Sci. 138, 234-248 (2014
58. Pederson, L., Hagedorn, P. H., Lindholm, M. W. and Lindow, M. A kinetic model explains why shorter and less affine enzyme-recruiting oligonucleotides can be more potent. Mol. Ther. Nucleic Acids 3, e149 (2014
59. Kuwahara, H. et al. Efficient in vivo delivery of siRNA into brain capillary endothelial cells along with endogenous lipoprotein. Mol. Ther. 19, 2213-2221 (2011
60. Usui, S., Hara, Y., Hosaki, S. and Okazaki, M. A new on-line dual enzymatic method for simultaneous quantification of cholesterol and triglycerides in lipoproteins by HPLC. J. Lipid Res. 43, 805-814 (2002
61. Ishiguro, T. et al. The carboxy-terminal fragment of a1A calcium channel preferentially aggregates in the cytoplasm of human spinocerebellar ataxia type 6 Purkinje cells. Acta Neuropathol. 119, 447-464 (2010
62. Yamamoto, T. et al. Cholesterol-lowering action of BNA-based antisense oligonucleotides targeting PCSK9 in atherogenic diet-induced hypercholesterolemic mice. Mol. Ther. Nucleic Acids 1, e22 (2012