Cellular DNA and RNA are made up of ribo- and 2"-deoxyribonucleic acids linked together via 3"-5" phosphodiester linkages and by far comprise the bulk of polynucleic acids found in cells. Much less common are oligonucleotides which have 2"-5" linkages. However, a unique feature of 2"-5" linked oligonucleotides is their ability to bind selectively to complementary RNA. These features suggest a number of interesting uses for 2"-5" linked oligos such as their use as RNA specific probes or in antisense oligos. Recently, oligos have been synthesized using 3"-deoxy-2"-phosphoramidites and 2"-deoxy-3"-phosphoramidites to produce chimeras with 2"-5" linked ends and 3"-5" linked central regions. It was found that 2"-5" phosphorothioate oligos: 1) bind selectively to complementary RNA with the same affinity as phosphodiester oligos; 2) exhibit much less nonspecific binding to cellular proteins; 3) do not activate RNase H. A 3"-deoxynucleoside at the 3"-terminus of an otherwise normal oligonucleotide effectively blocks polymerase extension.