Synthesis and in vitro inhibition properties of siRNA conjugates carrying glucose and galactose with different presentations.
Oligoribonucleotide conjugates and the corresponding siRNA duplexes against tumor necrosis factor carrying one, two, or four glucose and galactose residues at the 5'-end have been prepared using phosphoramidite chemistry. Carbohydrate-modified siRNA duplexes have similar inhibitory properties than unmodified RNA duplexes in HeLa cells transfected with oligofectamine. When HeLa cells were treated with siRNA carrying one, two, or four glucose residues without oligofectamine, no inhibition was observed. The inhibitory properties of siRNA carrying galactose residues without transfecting agent were tested on HuH-7 cells that have abundant asialoglycoprotein receptors. In these cells siRNA carrying galactose residues have slight anti-TNF inhibitory properties (25% in the best case) that are eliminated if the receptors are blocked with a competitor. These results demonstrate receptor-mediated uptake of siRNA carrying galactose residues, although the efficacy of the process is not enough for efficient RNA interference experiments.
Institute for Research in Biomedicine (IRB Barcelona), Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Baldiri Reixac 10, 08028 Barcelona, Spain.
Anna
A
Aviñó
Sandra M
SM
Ocampo
Ricardo
R
Lucas
José J
JJ
Reina
Juan Carlos
JC
Morales
José Carlos
JC
Perales
Ramon
R
Eritja
D045744:Cell Line, Tumor; D015195:Drug Design; D005690:Galactose / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000737:chemistry / Q000235:genetics*
D008055:Lipids; D009943:Organophosphorus Compounds; D034741:RNA, Small Interfering; D048069:Tumor Necrosis Factors; C484027:oligofectamine; C434331:phosphoramidite; D005947:Glucose; D005690:Galactose
Antisense Nucleic Acid Drug Dev. 1997 Jun;7(3):141-9
9212904
Bioconjug Chem. 2009 Jan;20(1):5-14
19053311
Bioconjug Chem. 2002 Sep-Oct;13(5):1071-8
12236789
Bioconjug Chem. 2003 Jan-Feb;14(1):239-46
12526714
Angew Chem Int Ed Engl. 2000 Oct 16;39(20):3660-3
11091431
Chemistry. 2008;14(26):7828-35
18637649
J Med Chem. 1995 Apr 28;38(9):1538-46
7739012
J Am Chem Soc. 2005 Feb 16;127(6):1624-5
15700981
Curr Drug Targets. 2005 Sep;6(6):647-53
16178798
Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):12982-7
17652171
Bioconjug Chem. 2003 Jan-Feb;14(1):18-29
12526688
Bioorg Med Chem Lett. 2004 Jun 7;14(11):2839-42
15125943
Glycoconj J. 2007 Apr;24(2-3):107-23
17268860
Bioconjug Chem. 2010 Jul 21;21(7):1280-7
20590107
Nat Chem Biol. 2006 Dec;2(12):711-9
17108989
Bioconjug Chem. 2004 Jul-Aug;15(4):890-6
15264878
Org Biomol Chem. 2004 Jul 7;2(13):1879-86
15227540
Clin Exp Pharmacol Physiol. 2006 May-Jun;33(5-6):533-40
16700890
Curr Opin Chem Biol. 2006 Dec;10(6):607-14
17049298
Farmaco. 2003 Mar;58(3):243-58
12620420
Methods Enzymol. 2005;392:278-96
15644187
Bioconjug Chem. 2009 Jun;20(6):1065-94
19175328
Med Res Rev. 2010 Mar;30(2):270-89
19626595
Bioconjug Chem. 2008 Jan;19(1):290-8
17850109
Curr Med Chem. 2005;12(19):2193-214
16178780
J Mol Biol. 2003 Apr 4;327(4):761-6
12654261
Carbohydr Res. 2009 Nov 2;344(16):2137-43
19765694
Chem Biodivers. 2004 Oct;1(10):1401-17
17191787
J Org Chem. 2009 Feb 6;74(3):1218-22
19123843
Bioorg Med Chem. 2001 Nov;9(11):2969-78
11597478