Novel Lipid-Oligonucleotide Conjugates Containing Long-Chain Sulfonyl Phosphoramidate Groups: Synthesis and Biological Properties
A. Sh. Derzhalova, Oleg V. Markov, А. А. Фокина, Yasuo Shiohama, Timofei S. Zatsepin, Masayuki Fujii, Marina A. Zenkova, Dmitry A. Stetsenko
Abstract
New lipid conjugates of DNA and RNA incorporating one to four [(4-dodecylphenyl)sulfonyl]phosphoramidate or (hexadecylsulfonyl)phosphoramidate groups at internucleotidic positions near the 3′ or 5′-end were synthesized and characterized. Low cytotoxicity of the conjugates and their ability to be taken up into cells without transfection agents were demonstrated. Lipid-conjugated siRNAs targeting repulsive guidance molecules a (RGMa) have shown a comparable gene silencing activity in PK-59 cells to unmodified control siRNA when delivered into the cells via Lipofectamine mediated transfection.
Topics & Concepts
PhosphoramidateOligonucleotideSulfonylTransfectionLipofectamineChemistryConjugated systemCytotoxicityConjugateSmall interfering RNABiochemistryCombinatorial chemistryDNAIn vitroGeneOrganic chemistryPolymerAlkylRecombinant DNAMathematicsVector (molecular biology)Mathematical analysisRNA Interference and Gene DeliveryAdvanced biosensing and bioanalysis techniquesDNA and Nucleic Acid Chemistry