A new and convenient synthesis method has been developed for coupling a ligand (e.g. PEG, peptides) through a cleavable disulfide linkage to an oligonucleotide at the 2´ position of a ribose ring. The resulting oligonucleotide conjugates are taken up efficiently into cells without the need for a transfection agent, and the 2´ OH group modification has a positive impact on stability, allowing natural (phosphodiester) oligonucleotide sequences to be used. Preliminary in vitro experiments have demonstrated effective target gene down-regulation.
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