| 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
|
|
WOS Category
|
PHYSICS, APPLIED
MATERIALS SCIENCE, MULTIDISCIPLINARY
PHYSICS, CONDENSED MATTER
CHEMISTRY, PHYSICAL
|
| Resource |
| DNA material |
pCAcc-Luc+ (RDB02443) |
