4′-Thio-β-D-oligoribonucleotides (12 mer and 16 mer) containing a mixed base sequence were synthesized via the phosphoramidite solid support approach. These RNA analogs showed very good nuclease resistance as compared with wild-type RNA. Furthermore, 4′-thio-β-D-oligoribonucleotides were shown to hybridize with a complementary DNA or RNA strand to form a duplex or with a DNA hairpin to form a triple helix. 4′-Thio-RNA binds more tightly to its complementary RNA strand than to its complementary DNA strand. A 4′-thio-RNA:RNA duplex is as stable as a 2′-O-methyl-RNA:RNA duplex. 4′-Thio-RNA, however, forms a 4′thio-RNA:DNA:DNA triplex with a stability similar to the corresponding triplex with al