Efficient gene regulation by PPAR gamma and thiazolidinediones in skeletal muscle and heart.
Mol Ther
; 6(2): 265-71, 2002 Aug.
Article
em En
| MEDLINE
| ID: mdl-12161194
ABSTRACT
We have developed a new gene regulation system for gene therapy. This system consists of two expression cassettes; one expresses the human peroxisome proliferator-activated receptor gamma(PPAR gamma), and the other expresses the therapeutic gene under the control of multiple peroxisome proliferator-activated receptor (PPAR) response elements (PPREs) linked to a basal promoter. Using direct injection of plasmid DNA into skeletal muscle or myocardium of rodents and oral administration of clinically approved PPAR gamma activators, we demonstrate that reporter gene expression can be induced more than 25-fold. We show that oral administration of PPAR gamma activator at intervals separated by several months results in repeated pulses of high-level reporter gene expression. We also document a PPAR gamma activator dose-response effect on reporter gene expression. This is the first report of a gene regulation system that makes use of a human transcription factor and that may be safer than chimeric transcription factors for human gene therapy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiazóis
/
Fatores de Transcrição
/
Regulação da Expressão Gênica
/
Receptores Citoplasmáticos e Nucleares
/
Tiazolidinedionas
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article