title: Ocular gene delivery systems using ternary complexes of plasmid DNA, polyethylenimine, and anionic polymers.
abstract: In this experiment, we developed anionic ternary complexes for effective and safe ocular gene delivery. Ternary complexes were constructed by coating plasmid DNA (pDNA)/polyethylenimine (PEI) complex with anionic polymers such as γ-polyglutamic acid (γ-PGA) and chondroitin sulfate (CS). The cationic pDNA/PEI complex showed high gene expression on the human retinal pigment epithelial cell line, ARPE-19 cells. The pDNA/PEI complexes, however, also showed high cytotoxicity on the cells and aggregated strongly in the vitreous body. On the other hand, the anionic ternary complexes showed high gene expression on ARPE-19 cells without such cytotoxicity and aggregation. After intravitreous administration of the complexes, the anionic ternary complexes showed high gene expression in the retina. These results strongly indicate that anionic ternary complexes are suitable for effective and safe ocular gene therapy.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46–29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606–8501, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Uematsu
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Shimoda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Suzuma
authors.forename: Masato
authors.initials: M
authors.lastname: Nakai
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitaoka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002809:Chondroitin Sulfates / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D010957:Plasmids; D011094:Polyethyleneimine / Q000737:chemistry; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D011817:Rabbits; D014822:Vitreous Body / Q000378:metabolism
chemical_list: C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D011094:Polyethyleneimine; D002809:Chondroitin Sulfates; D004247:DNA