RRC ID 2010
Author Nishiyama N, Iriyama A, Jang WD, Miyata K, Itaka K, Inoue Y, Takahashi H, Yanagi Y, Tamaki Y, Koyama H, Kataoka K.
Title Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer.
Journal Nat Mater
Abstract 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.
Volume 4(12)
Pages 934-41
Published 2005-12-1
DOI 10.1038/nmat1524
PII nmat1524
PMID 16299510
MeSH Animals Conjunctiva / metabolism DNA / genetics* DNA / ultrastructure Dendrimers / chemistry* Endocytosis Flow Cytometry Fluoresceins / pharmacology Fluorescent Dyes / pharmacology Gene Transfer Techniques* Genes, Reporter HeLa Cells Humans Indoles / chemistry* Isoindoles Light Luciferases / metabolism Male Microscopy, Atomic Force Models, Biological Octanols / chemistry Photosensitizing Agents / chemistry* Rats Rats, Wistar Scattering, Radiation Static Electricity Transgenes Water / chemistry
IF 38.663
Times Cited 270
DNA material pCAcc-Luc+ (RDB02443)