Steroid and lipid conjugates of siRNAs to enhance cellular uptake and gene silencing in liver cells

/Home/Biologics Delivery - Protein Synthesis/RNA - Protein Synthesis/siRNA - Protein Synthesis/siRNA Conjugates - Protein Synthesis

Steroid and lipid conjugates of siRNAs to enhance cellular uptake and gene silencing in liver cells
Oct 2004
Christina Lorenz, Philipp Hadwiger, Matthias John, et. al.
Bioorg Med Chem Lett
Double-stranded short interfering RNAs (siRNAs) mediate post-transcriptional inhibition of gene expression in a variety of biological systems. However, human liver cells show poor uptake of these nucleic acids. In order to improve the delivery of siRNA into these cells without transfection agents, we have synthesized two series of lipophilic siRNAs conjugated with derivatives of cholesterol, lithocholic acid or lauric acid. The lipid moieties were covalently linked to the 5'-ends of the RNAs using phosphoramidite chemistry. The potency of these chemically modified siRNAs to inhibit reporter gene expression was further investigated in vitro with beta-galactosidase expressing liver cells.