期刊
MOLECULAR DIVERSITY
卷 15, 期 3, 页码 751-757出版社
SPRINGER
DOI: 10.1007/s11030-011-9305-6
关键词
siRNA; Oligonucleotide-carbohydrate conjugates; RNA interference; Tumor necrosis factor; Oligonucleotide synthesis
类别
资金
- CSIC [PIF06-045]
- Spanish Ministry of Education [BFU2007-63287, CTQ2006-01123, CTQ2010-20541, CTQ2009-13705]
- Generalitat de Catalunya [2009/SGR/208]
- Iniciativa Ingenio
- European Regional Development Fund
- CSIC
- VI National RDi Plan
- CIBER
- Instituto de Salud Carlos III
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.
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