INTEGRIN RECEPTOR-TARGETED TRANSFER PEPTIDES FOR EFFICIENT DELIVERY OF ANTISENSE OLIGODEOXYNUCLEOTIDES

Integrin receptor-targeted transfer of oligodeoxynucleotides (ODNs) by small synthetic peptides was used for improving delivery of antisense ODNs. An 18-mer phosphodiester bond containing ODN complementary to c -myb-encoded mRNA was complexed with several transfer peptides, contai ning as their parts two modules: (a) an RGD-motif as targeting sequenc e for integrin receptor and (b) nucleocapsid protein (NCp) 7 of HIV-1 or NCp7-derived peptides for complex formation with the ODNs. The amou nt of antisense ODN required for the inhibition of proliferation of hu man myeloid cell line HL-60 in vitro can be more than 50-fold reduced by complexing with transfer peptides. The efficiency of antisense deli very was increased by multimerization of the targeting sequence for th e integrin receptor. Competition with integrin peptide abolished the e ffect, indicating that the integrin receptor is indeed responsible for the reaction.