HELIX-STABILIZING AGENT, CC-1065, ENHANCES SUPPRESSION OF TRANSLATIONBY AN ANTISENSE OLIGODEOXYNUCLEOTIDE

The antitumor antibiotic CC-1065 is known to bind at selected sequence s in the minor groove of duplex nucleic acids and to hyperstabilize th e duplexes against thermal melting. These properties suggested that CC -1065 may enhance translation inhibition by antisense oligonucleotides directed against a specific mRNA. A 585 bp mRNA transcript containing the equine infectious anemia virus (EIAV) 52 gene and a portion of th e env gene was prepared. Also, a complementary 20 mer antisense oligod eoxynucleotide (5'-TGTTGGGTAATAGG-GGTTGA-3') was prepared against a ta rget sequence in the mRNA located near the translational initiation si tes of the overlapping S2 and env genes. The center of the target sequ ence had an expected CC-1065 recognition sequence (5'-UAUUA-3'). Trans lation in the presence of CC-1065;Ind antisense was markedly suppresse d compared with that of antisense alone. Addition of a sense 20 mer st rand, with or without CC-1065, had little or no effect on translation. CC-1065 and related compounds may be useful as ligands for enhancing the stability of sense-antisense duplexes and for promoting the inhibi tion of translation by antisense oligonucleotides.