Oligodeoxynucleotide analogs as informational drugs to regulate translation

Of the chemically modified backbone analogs of oligodeoxynucleotides that have been developed for antisense applications, the phosphorothioate (PS) analog has perhaps the best properties. Nevertheless, it also has certain disadvantages, notably reduced hybridization and increased non-selective inhibition of translation, compared to the natural phosphodiester (PO) compounds. We have therefore synthesized and characterized a series of co-polymers, with the same antisense beta-globin sequence, but with different repeated sequences of PO and PS and tested them for their comparative properties. The results indicate that a PO-PS co-polymer is the best backbone modification for an antisense compound.