Described are 5’-cyclo-phosphonate modified nucleotides, and oligonucleotides, such as interference (RNAi) agents, containing 5’-cyclo-phosphonate modified nucleotides. The RNAi agents having either double-stranded or single-stranded oligonucleotides described herein comprising 5’cyclo-phosphonate modified nucleotides are useful in modulating gene expression as well as therapeutic, diagnostic, target validation, and genomic discovery applications. The RNAi agents and single-stranded antisense oligonucleotides comprising 5’-cyclo-phosphonate modified nucleotides are useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.本發明闡述5’-環-磷酸修飾之核苷酸及含有5’-環-磷酸修飾之核苷酸之寡核苷酸(例如干擾(RNAi)劑)。本文中所闡述包含5’環-磷酸修飾之核苷酸之具有雙鏈或單鏈寡核苷酸之該等RNAi劑可用於調節基因表現以及治療、診斷、靶標驗證及基因體發現應用。包含5’-環-磷酸修飾之核苷酸之該等RNAi劑及單鏈反義寡核苷酸可用於治療對細胞、組織或生物體中基因表現或活性之抑制有反應之疾病或病狀。