siRNA Conjugates Carrying Sequentially Assembled Trivalent N-Acetylgalactosamine Linked Through Nucleosides Elicit Robust Gene Silencing In Vivo in Hepatocytes

ACS Chemical Biology

Volumn 10, Issue 5, 2015, Pages 1181-1187

  Matsuda, Shigeo ^a   Keiser, Kristofer ^a   Nair, Jayaprakash K ^a   Charisse, Klaus ^a   Manoharan, Rajar M ^a   Kretschmer, Philip ^a   Peng, Chang G ^a   Kel'in, Alexander V ^a   Kandasamy, Pachamuthu ^a   Willoughby, Jennifer L S ^a   Liebow, Abigail ^a   Querbes, William ^a   Yucius, Kristina ^a   Nguyen, Tuyen ^a   Milstein, Stuart ^a   Maier, Martin A ^a   Rajeev, Kallanthottathil G ^a   Manoharan, Muthiah ^a  

^a ALNYLAM PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASIALOGLYCOPROTEIN RECEPTOR; MONOMER; N ACETYLGALACTOSAMINE; NUCLEOSIDE; SMALL INTERFERING RNA; SUGAR;

ANIMAL CELL; ARTICLE; CONJUGATE; CONTROLLED STUDY; COST EFFECTIVENESS ANALYSIS; EVALUATION STUDY; GENE SILENCING; IN VITRO STUDY; IN VIVO STUDY; LIVER CELL; MOLECULAR RECOGNITION; MOUSE; NONHUMAN; PRIORITY JOURNAL; SYNTHESIS; ANIMAL; C57BL MOUSE; GENETICS; METABOLISM;

ACETYLGALACTOSAMINE; ANIMALS; GENE SILENCING; HEPATOCYTES; MICE; MICE, INBRED C57BL; NUCLEOSIDES; RNA, SMALL INTERFERING;

EID: 84929574453     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb501028c     Document Type: Article

References (25)

1. Bumcrot, D., Manoharan, M., Koteliansky, V., and Sah, D. W. Y. (2006) RNAi therapeutics: a potential new class of pharmaceutical drugs Nat. Chem. Biol. 2, 711 - 719
2. Deleavey, G. F. and Damha, M. J. (2012) Designing Chemically Modified Oligonucleotides for Targeted Gene Silencing Chem. Biol. 19, 937 - 954
3. Novina, C. D. and Sharp, P. A. (2004) The RNAi revolution Nature 430, 161 - 164
4. Joshi, B. H. and Pachchigar, K. P. (2014) siRNA: novel therapeutics from functional genomics Biotechnol. Genet. Eng. Rev. 30, 1 - 30
5. Karunapriyachitra, Ramadevibhimavarapu, Srinath, N., Sabasu, N., Mahesh, B., and Balavamsikrishna (2013) siRNA-an excellent technique for downregulation of gene expression Int. J. Invent. Pharm. Sci. 1, 6 - 14
6. Li, T., Wu, M., Zhu, Y. Y., Chen, J., and Chen, L. (2014) Development of RNA Interference-Based Therapeutics and Application of Multi-Target Small Interfering RNAs Nucleic Acid Ther. 24, 302 - 312
7. Nielsen, C., Kjems, J., Sorensen, K. R., Engelholm, L. H., and Behrendt, N. (2014) Advances in targeted delivery of small interfering RNA using simple bioconjugates Expert Opin. Drug Delivery 11, 791 - 822
8. Soni, R. S., Gohil, A., and Avachat, A. M. (2013) Delivering small interfering RNA for novel therapeutics Int. Pharm. Sci. 3, 11 - 19 19 pp.
9. Meier, M., Bider, M. D., Malashkevich, V. N., Spiess, M., and Burkhard, P. (2000) Crystal Structure of the Carbohydrate Recognition Domain of the H1 Subunit of the Asialoglycoprotein Receptor J. Mol. Biol. 300, 857 - 865
10. Grewal, P. K. (2010) The Ashwell-Morell receptor Methods Enzymol. 479, 223 - 241
11. Spiess, M. (1990) The asialoglycoprotein receptor: a model for endocytic transport receptors Biochemistry 29, 10009 - 10018
12. Nair, J. K., Willoughby, J. L. S., Chan, A., Charisse, K., Alam, M. R., Wang, Q., Hoekstra, M., Kandasamy, P., Kel'in, A. V., Milstein, S., Taneja, N., O'Shea, J., Shaikh, S., Zhang, L., van der Sluis, R. J., Jung, M. E., Akinc, A., Hutabarat, R., Kuchimanchi, S., Fitzgerald, K., Zimmermann, T., van Berkel, T. J. C., Maier, M. A., Rajeev, K. G., and Manoharan, M. (2014) Multivalent N-Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing J. Am. Chem. Soc. 136, 16958 - 16961
13. Lonnberg, H. (2009) Solid-Phase Synthesis of Oligonucleotide Conjugates Useful for Delivery and Targeting of Potential Nucleic Acid Therapeutics Bioconjugate Chem. 20, 1065 - 1094
14. Spinelli, N., Defrancq, E., and Morvan, F. (2013) Glycoclusters on oligonucleotide and PNA scaffolds: synthesis and applications Chem. Soc. Rev. 42, 4557 - 4573
15. http://www.alnylam.com/capella/presentations/positive-initial-revusiran-phase-2-data/.
16. Prakash, T. P., Graham, M. J., Yu, J., Carty, R., Low, A., Chappell, A., Schmidt, K., Zhao, C., Aghajan, M., Murray, H. F., Riney, S., Booten, S. L., Murray, S. F., Gaus, H., Crosby, J., Lima, W. F., Guo, S., Monia, B. P., Swayze, E. E., and Seth, P. P. (2014) Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice Nucleic Acids Res. 42, 8796 - 8807
17. Meade, B. R., Gogoi, K., Hamil, A. S., Palm-Apergi, C., Berg, A. v. d., Hagopian, J. C., Springer, A. D., Eguchi, A., Kacsinta, A. D., Dowdy, C. F., Presente, A., Lonn, P., Kaulich, M., Yoshioka, N., Gros, E., Cui, X.-S., and Dowdy, S. F. (2014) Efficient delivery of RNAi prodrugs containing reversible charge-neutralizing phosphotriester backbone modifications Nat. Biotechnol. 32, 1256 - 1261
18. http://ir.regulusrx.com/releasedetail.cfm?ReleaseID=877462.
19. Yamada, T., Peng, C. G., Matsuda, S., Addepalli, H., Jayaprakash, K. N., Alam, M. R., Mills, K., Maier, M. A., Charisse, K., Sekine, M., Manoharan, M., and Rajeev, K. G. (2011) Versatile Site-Specific Conjugation of Small Molecules to siRNA Using Click Chemistry J. Org. Chem. 76, 1198 - 1211
20. Manoharan, M., Tivel, K. L., Andrade, L. K., and Cook, P. D. (1995) 2′-O- and 3′-O-pyrimidine amino-tether-containing oligodeoxyribonucleotides: synthesis and conjugation chemistry Tetrahedron Lett. 36, 3647 - 3650
21. Carlile, T. M., Rojas-Duran, M. F., Zinshteyn, B., Shin, H., Bartoli, K. M., and Gilbert, W. V. (2014) Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells Nature 515, 143 - 146
22. Manoharan, M., Rajeev, K. G., Kelin, A. V., Takkellapati, S. R., and Matsuda, S. Nucleotides modified at the 2′-position of the sugar moiety for use in nucleic acids for therapeutic use. PCT Int. Appl. WO 2010101951, 2010.
23. Ramzaeva, N., Rosemeyer, H., Leonard, P., Muhlegger, K., Bergmann, F., Von der Eltz, H., and Seela, F. (2000) Oligonucleotides functionalized by fluorescein and rhodamine dyes: Michael addition of methyl acrylate to 2′-deoxypseudouridine Helv. Chim. Acta 83, 1108 - 1126
24. Severgnini, M., Sherman, J., Sehgal, A., Jayaprakash, N. K., Aubin, J., Wang, G., Zhang, L., Peng, C. G., Yucius, K., Butler, J., and Fitzgerald, K. (2012) A rapid two-step method for isolation of functional primary mouse hepatocytes: cell characterization and asialoglycoprotein receptor based assay development Cytotechnology 64, 187 - 195
25. Rajeev, K. G., Nair, J. K., Jayaraman, M., Charisse, K., Taneja, N., O'Shea, J., Willoughby, J. L. S., Yucius, K., Nguyen, T., Shulga-Morskaya, S., Milstein, S., Liebow, A., Querbes, W., Borodovsky, A., Fitzgerald, K., Maier, M. A., and Manoharan, M. (2015) Hepatocyte-Specific Delivery of siRNA Conjugated to Novel Non-Nucleosidic Trivalent N -Acetylgalactosamine Elicits Robust Gene Silencing In Vivo ChemBioChem 10.1002/cbic.201500023