This invention relates to a process for introducing two or more 2′-modifications into an RNA, wherein the RNA has a 2′-O substituent containing an alkyl ester functional group on one or more ribose rings of a strand and a 2′-O substituent containing an alkyne functional groups on one or more ribose rings on the same strand. The process comprises a) adding an amine compound to the RNA to form amidation reactions with the alkyl ester functional groups; b) dissolving the modified RNA from step (a) in a solvent to form a solution; and c) adding an organic azide and a copper or ruthenium catalyst to the solution obtained in step (b) to form 2′-azide-alkyne cycloaddition reaction products with the alkyne functional groups.