title: Secure splenic delivery of plasmid DNA and its application to DNA vaccine.
abstract: In this experiment, we developed a novel safe and effective gene delivery vector coated with γ-polyglutamic acid (γ-PGA-coated complexes). The γ-PGA-coated complex was composed of chiseled spherical nano-particles with anionic charges. The plasmid DNA/polyethyleneimine complex (non-coated complex) showed high transgene efficiency in the spleen and lung after intravenous administration in mice, with high liver toxicity and lethality. On the other hand, γ-PGA-coated complex selectively showed high transgene efficiency in the spleen without such toxicity. Furthermore, the γ-PGA-coated complex highly accumulated and showed high gene expression in the marginal zone of the spleen. Those results strongly indicated that γ-PGA-coated complex was suitable as a DNA vaccine vector. We therefore applied γ-PGA-coated complex to melanoma DNA vaccine, pUb-M. The γ-PGA-coated complex containing pUb-M significantly inhibited the growth and metastasis of a melanoma cell line, B16-F10 cells. In conclusion, we developed a splenic gene vector, γ-PGA-coated complex, as a novel technology for clinical vaccination.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Muro
authors.forename: Norihide
authors.initials: N
authors.lastname: Higuchi
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Mana
authors.initials: M
authors.lastname: Miyakoda
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Yui
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D018014:Gene Transfer Techniques; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology; D013154:Spleen / Q000378:metabolism*; D019444:Vaccines, DNA
chemical_list: D019496:Cancer Vaccines; D019444:Vaccines, DNA; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases