Specific inhibition of mRNA translation by complementary oligonucleotides covalently linked to intercalating agents.

Synthetic oligodeoxynucleotides that are covalently linked at their 3' end to an acridine derivative and are complementary to the repeated sequence UUAAAUUAAAUUAAA adjacent to the ribosome binding site of the gene 32-encoded mRNA from phage T4 have been used to regulate the synthesis of gene 32-encoded protein in vitro. These modified, synthetic oligonucleotides specifically block the translation of gene 32-encoded mRNA with a higher efficiency than the homologous unsubstituted oligonucleotides. The inhibition produced by these short "anti-messengers" is due to the formation of specific mRNA . oligodeoxynucleotide hybrids that are stabilized by the intercalation of the acridine ring in the RNA . DNA duplex.