Improved gene expression in resting macrophages using an oligopeptide derived from Vpr of human immunodeficiency virus type-1.
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.
Mizoguchi
Izuru
I
Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Ooe
Yoshihiro
Y
Hoshino
Shigeki
S
Shimura
Mari
M
Kasahara
Tadashi
T
Kano
Shigeyuki
S
Ohta
Toshiko
T
Takaku
Fumimaro
F
Nakayama
Yasuhide
Y
Ishizaka
Yukihito
Y
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
D016336:Gene Products, vpr; D010446:Peptide Fragments; D054325:vpr Gene Products, Human Immunodeficiency Virus; D004247:DNA