The phosphorodithioate linkage (PS2) is both achiral and essentially resistant to nucleases. Previous studies have shown very interesting results which include observations that DNA with PS2 linkages activates RNase H in vitro, strongly inhibits human immunodeficiency virus (HIV) reverse transcriptase, induces B-cell proliferation and differentiation, and is completely resistant to hydrolysis by various nucleases. 2’-OMe- RNA Thiophosphoramidites are RNA monomers designed to produce oligos combining the PS2 linkage with the 2’-O-methyl ribose modification. These PS2-modified RNA oligos have potential for use in siRNAs and dithiophosphate aptamers (thioaptamers).