title: Improved gene expression in resting macrophages using an oligopeptide derived from Vpr of human immunodeficiency virus type-1.
abstract: Vpr, an accessory gene product of human immunodeficiency virus type-1, is thought to transport a viral DNA from the cytoplasm to the nucleus in resting macrophages. Previously, we reported that a peptide encompassing amino acids 52-78 of Vpr (C45D18) promotes the nuclear trafficking of recombinant proteins that are conjugated with C45D18. Here, we present evidence that C45D18, when conjugated with a six-branched cationic polymer of poly(N,N-dimethylaminopropylacrylamide)-block-oligo(4-aminostyrene) (SV: star vector), facilitates gene expression in resting macrophages. Although there was no difference between SV alone and C45D18-SV with respect to gene transduction into growing cells, C45D18-SV resulted in more than 40-fold greater expression of the exogenous gene upon transduction into chemically differentiated macrophages and human quiescent monocyte-derived macrophages. The data suggest that C45D18 contributes to improving the ability of a non-viral vector to transduce macrophages with exogenous genes and we discuss its further application.
authors.affiliation: Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
authors.forename: Izuru
authors.initials: I
authors.lastname: Mizoguchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ooe
authors.forename: Shigeki
authors.initials: S
authors.lastname: Hoshino
authors.forename: Mari
authors.initials: M
authors.lastname: Shimura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kano
authors.forename: Toshiko
authors.initials: T
authors.lastname: Ohta
authors.forename: Fumimaro
authors.initials: F
authors.lastname: Takaku
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Ishizaka
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D016336:Gene Products, vpr / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D016336:Gene Products, vpr; D010446:Peptide Fragments; D054325:vpr Gene Products, Human Immunodeficiency Virus; D004247:DNA