Disclosed herein are oligonucleotides, such as nucleic acid inhibitor molecules, having a 4-phosphate analog and methods of using the same, for example, to modulate the expression of a target gene in a cell. The phosphate analogs are bound to the 4-carbon of the sugar moiety (e.g., a ribose or deoxyribose or analog thereof) of the 5-terminal nucleotide of an oligonucleotide. Typically, the phosphate analog is an oxymethylphosphonate, where the oxygen atom of the oxymethyl group is bound to the 4-carbon of the sugar moiety or analog thereof.
