Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer.
The control of gene transfection in the body is a core issue in gene therapy. Photochemical internalization is a technology that allows light-induced delivery of DNA, drugs or other biological factors directly inside cells. Usually it requires that a photosensitizer be added to the drug-delivery system to photochemically destabilize the endosomal membrane. Here we present a system for in vivo DNA delivery in which these two components are assembled into one structure. This is a ternary complex composed of a core containing DNA packaged with cationic peptides and enveloped in the anionic dendrimer phthalocyanine, which provides the photosensitizing action. The ternary complex showed more than 100-fold photochemical enhancement of transgene expression in vitro with reduced photocytotoxicity. In an animal experiment, subconjuctival injection of the ternary complex followed by laser irradiation resulted in transgene expression only in the laser-irradiated site. This work demonstrates a new biomedical application for dendrimers, and the first success in the photochemical-internalization-mediated gene delivery in vivo.
Nishiyama
Nobuhiro
N
Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Iriyama
Aya
A
Jang
Woo-Dong
WD
Miyata
Kanjiro
K
Itaka
Keiji
K
Inoue
Yuji
Y
Takahashi
Hidenori
H
Yanagi
Yasuo
Y
Tamaki
Yasuhiro
Y
Koyama
Hiroyuki
H
Kataoka
Kazunori
K
D000818:Animals; D003228:Conjunctiva / Q000378:metabolism; D004247:DNA / Q000235:genetics* / Q000648:ultrastructure; D050091:Dendrimers / Q000737:chemistry*; D004705:Endocytosis; D005434:Flow Cytometry; D005452:Fluoresceins / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D054833:Isoindoles; D008027:Light; D008156:Luciferases / Q000378:metabolism; D008297:Male; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D000442:Octanols / Q000737:chemistry; D017319:Photosensitizing Agents / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012542:Scattering, Radiation; D055672:Static Electricity; D019076:Transgenes; D014867:Water / Q000737:chemistry
D050091:Dendrimers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007211:Indoles; D054833:Isoindoles; D000442:Octanols; D017319:Photosensitizing Agents; D014867:Water; D004247:DNA; D008156:Luciferases; C013647:phthalocyanine