Efficient Synthesis and Biological Evaluation of 5′-GalNAc Conjugated Antisense Oligonucleotides

Bioconjugate Chemistry

Volumn 26, Issue 8, 2015, Pages 1451-1455

  Østergaard, Michael E ^a   Yu, Jinghua ^a   Kinberger, Garth A ^a   Wan, W Brad ^a   Migawa, Michael T ^a   Vasquez, Guillermo ^a   Schmidt, Karsten ^a   Gaus, Hans J ^a   Murray, Heather M ^a   Low, Audrey ^a   Swayze, Eric E ^a   Prakash, Thazha P ^a   Seth, Punit P ^a  

^a ISIS PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SYNTHESIS (CHEMICAL);

ANTISENSE OLIGONUCLEOTIDES; BIOLOGICAL EVALUATION; EFFICIENT SYNTHESIS; HEPATOCYTES; N-ACETYL GALACTOSAMINE; PHASE CONJUGATIONS; SOLID SUPPORTS; SOLUTION PHASE; SOLUTION PHASE METHODS; SYNTHESIS EVALUATION;

OLIGONUCLEOTIDES;

5' HEXYLAMINO MODIFIED ANTISENSE OLIGONUCLEOTIDE; ANTISENSE OLIGONUCLEOTIDE; N ACETYLGALACTOSAMINE; UNCLASSIFIED DRUG;

ARTICLE; BIOASSAY; DRUG CONJUGATION; DRUG POTENCY; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NONHUMAN; STRUCTURE ACTIVITY RELATION; ANIMAL; C57BL MOUSE; CELL CULTURE; CHEMISTRY; CYTOLOGY; DRUG EFFECTS; EVALUATION STUDY; LIVER; LIVER CELL; MOUSE; SYNTHESIS;

ANIMALIA;

ACETYLGALACTOSAMINE; ANIMALS; CELLS, CULTURED; HEPATOCYTES; LIVER; MICE; MICE, INBRED C57BL; OLIGONUCLEOTIDES, ANTISENSE;

EID: 84939800605     PISSN: 10431802     EISSN: 15204812     Source Type: Journal    
DOI: 10.1021/acs.bioconjchem.5b00265     Document Type: Article

References (22)

1. Bennett, C. F. and Swayze, E. E. (2010) RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform Annu. Rev. Pharmacol. Toxicol. 50, 259-93
2. Monia, B. P., Lesnik, E. A., Gonzalez, C., Lima, W. F., McGee, D., Guinosso, C. J., Kawasaki, A. M., Cook, P. D., and Freier, S. M. (1993) Evaluation of 2′-modified oligonucleotides containing 2′-deoxy gaps as antisense inhibitors of gene expression J. Biol. Chem. 268, 14514-22
3. Crooke, S. T. and Geary, R. S. (2013) Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B Br. J. Clin. Pharmacol. 76, 269-76
4. Kaur, H., Babu, B. R., and Maiti, S. (2007) Perspectives on chemistry and therapeutic applications of locked nucleic acid (LNA) Chem. Rev. 107, 4672-4697
5. Seth, P. P., Siwkowski, A., Allerson, C. R., Vasquez, G., Lee, S., Prakash, T. P., Wancewicz, E. V., Witchell, D., and Swayze, E. E. (2009) Short antisense oligonucleotides with novel 2′-4′ conformationally restricted nucleoside analogues show improved potency without increased toxicity in animals J. Med. Chem. 52, 10-3
6. Prakash, T. P., Graham, M. J., Yu, J., Carty, R., Low, A., Chappell, A., Schmidt, K., Zhao, C., Aghajan, M., and Murray, H. F. et al. 2014, Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice Nucleic Acids Res. 42, 8796-807
7. Nair, J. K., Willoughby, J. L., Chan, A., Charisse, K., Alam, M. R., Wang, Q., Hoekstra, M., Kandasamy, P., Kelin, A. V., and Milstein, S. et al. 2014, Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing J. Am. Chem. Soc. 136, 16958-61
8. Matsuda, S., Keiser, K., Nair, J. K., Charisse, K., Manoharan, R. M., Kretschmer, P., Peng, C. G., V. Kelin, A., Kandasamy, P., and Willoughby, J. L. S. et al. 2015, siRNA conjugates carrying sequentially assembled trivalent N-acetylgalactosamine linked through nucleosides elicit robust gene silencing in vivo in hepatocytes ACS Chem. Biol. 10.1021/cb501028c
9. Wong, S. C., Klein, J. J., Hamilton, H. L., Chu, Q., Frey, C. L., Trubetskoy, V. S., Hegge, J., Wakefield, D., Rozema, D. B., and Lewis, D. L. (2012) Co-injection of a targeted, reversibly masked endosomolytic polymer dramatically improves the efficacy of cholesterol-conjugated small interfering RNAs in vivo Nucleic Acid Ther. 22, 380-90
10. Meade, B. R., Gogoi, K., Hamil, A. S., Palm-Apergi, C., van den Berg, A., Hagopian, J. C., Springer, A. D., Eguchi, A., Kacsinta, A. D., and Dowdy, C. F. et al. 2014, Efficient delivery of RNAi prodrugs containing reversible charge-neutralizing phosphotriester backbone modifications Nat. Biotechnol. 32, 1256-61
11. Singh, Y., Spinelli, N., and Defrancq, E. (2008) Chemical strategies for oligonucleotide-conjugates synthesis Curr. Org. Chem. 12, 263-290
12. Antopolsky, M., Azhayeva, E., Tengvall, U., Auriola, S., Jaaskelainen, I., Ronkko, S., Honkakoski, P., Urtti, A., Lonnberg, H., and Azhayev, A. (1999) Peptide-oligonucleotide phosphorothioate conjugates with membrane translocation and nuclear localization properties Bioconjugate Chem. 10, 598-606
13. Turner, J. J., Arzumanov, A. A., and Gait, M. J. (2005) Synthesis, cellular uptake and HIV-1 Tat-dependent trans-activation inhibition activity of oligonucleotide analogues disulphide-conjugated to cell-penetrating peptides Nucleic Acids Res. 33, 27-42
14. Sanchez, A., Pedroso, E., and Grandas, A. (2012) Conjugation reactions involving maleimides and phosphorothioate oligonucleotides Bioconjugate Chem. 23, 300-7
15. Jirka, S. M., Heemskerk, H., Tanganyika-de Winter, C. L., Muilwijk, D., Pang, K. H., de Visser, P. C., Janson, A., Karnaoukh, T. G., Vermue, R., and t Hoen, P. A. et al. 2014, Peptide conjugation of 2′-O-methyl phosphorothioate antisense oligonucleotides enhances cardiac uptake and exon skipping in mdx mice Nucleic Acid Ther. 24, 25-36
16. Marzenell, P., Hagen, H., Blechinger, J., Erfle, H., and Mokhir, A. (2014) Terminally modified, short phosphorothioate oligonucleotides as inhibitors of gene expression in cells Bioorg. Med. Chem. Lett. 24, 4694-8
17. Basu, S. and Wickstrom, E. (1995) Solid phase synthesis of a d -peptide-phosphorothioate oligodeoxynucleotide conjugate from two arms of a polyethylene glycol-polystyrene support Tetrahedron Lett. 36, 4943-6
18. Diala, I., Osada, A., Maruoka, S., Imanisi, T., Murao, S., Ato, T., Ohba, H., and Fujii, M. (2007) Synthesis of phosphorothioate oligonucleotide-peptide conjugates by solid phase fragment condensation Bioorg. Med. Chem. Lett. 17, 6576-8
19. Green, M. and Berman, J. (1990) Preparation of pentafluorophenyl esters of Fmoc protected amino acids with pentafluorophenyl trifluoroacetate Tetrahedron Lett. 31, 5851-2
20. https://tools.lifetechnologies.com/content/sfs/manuals/mp00143.pdf.
21. Baenziger, J. U. and Fiete, D. (1980) Galactose and N-acetylgalactosamine-specific endocytosis of glycopeptides by isolated rat hepatocytes Cell 22, 611-620
22. Baenziger, J. U. and Maynard, Y. (1980) Human hepatic lectin. Physiochemical properties and specificity J. Biol. Chem. 255, 4607-4613