title: Integrin receptor-targeted transfer peptides for efficient delivery of antisense oligodeoxynucleotides.
abstract: 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, containing as their parts two modules: (a) an RGD-motif as targeting sequence for integrin receptor and (b) nucleocapsid protein (NCp) 7 of HIV-1 or NCp7-derived peptides for complex formation with the ODNs. The amount of antisense ODN required for the inhibition of proliferation of human myeloid cell line HL-60 in vitro can be more than 50-fold reduced by complexing with transfer peptides. The efficiency of antisense delivery was increased by multimerization of the targeting sequence for the integrin receptor. Competition with integrin peptide abolished the effect, indicating that the integrin receptor is indeed responsible for the reaction.
authors.affiliation: Institute of Medical Virology, University of Zurich, Switzerland.
authors.forename: A S
authors.initials: AS
authors.lastname: Bachmann
authors.forename: A
authors.initials: A
authors.lastname: Surovoy
authors.forename: G
authors.initials: G
authors.lastname: Jung
authors.forename: K
authors.initials: K
authors.lastname: Moelling
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins; D002455:Cell Division; D015683:Gene Products, gag / Q000378:metabolism*; D018014:Gene Transfer Techniques; D018922:HL-60 Cells; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators / Q000235:genetics*; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D036022:Capsid Proteins; D015683:Gene Products, gag; D016023:Integrins; C071884:NCP7 protein, Human immunodeficiency virus 1; D016376:Oligonucleotides, Antisense; D010455:Peptides; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus