Abstract: Disclosed are polynucleotide constructs having a strand linked to a moiety carrying one or more auxiliary moieties. Also disclosed are polynucleotide constructs interrupted with a sugar analogue, and polynucleotide constructs with stereochemical{circumflex over (?)} enriched phosphorothioates. The polynucleotide constructs may be provided as hybridized polynucleotide constructs. Also featured are methods of delivery a polynucleotide construct to a cell and methods of reducing the expression of a protein in a cell by contacting the cell with the disclosed polynucleotide construct or hybridized polynucleotide construct.

Abstract: Disclosed are chiral phosphoramidite auxiliary compositions for diastereoselective synthesis of stereochemically enriched oligonucleotides, and nucleoside phosphoramidite compounds comprising the same. Exemplary structures of the chiral phosphoramidite auxiliary compositions include Formulas (IA) and (IB).