Mx1 and IP-10: biomarkers to measure IFN-beta activity in mice following gene-based delivery.
J Interferon Cytokine Res
; 26(10): 699-705, 2006 Oct.
Article
em En
| MEDLINE
| ID: mdl-17032164
ABSTRACT
Recombinant interferon-beta (IFN-beta) protein is used successfully for the treatment of multiple sclerosis (MS). Gene therapy might be an alternative approach to overcome drawbacks occurring with IFN-beta protein therapy. A critical issue in developing a new approach is detection of biologically active IFN-beta in preclinical models. The goal of the present study was to determine if Mx1 and IP-10, which are known to be activated after IFN-beta treatment in humans, can be used as biomarkers in mice. In three in vivo experiments, the correlation between different methods of murine IFN-beta (MuIFN-beta) delivery and biomarker induction was studied (1) bolus protein delivery by intravenous (i.v.) or intramuscular (i.m.) injection, (2) gene-based delivery of IFN- beta by i.m. injection of plasmid DNA, followed by electroporation, and (3) gene-based delivery of IFN-beta by i.m. injection of adenovirus-associated type 1 (AAV1). Short-term induction of Mx1 mRNA and IP-10 was observed after treatment with bolus MuIFN-beta protein. Long-term induction of both biomarkers was observed after IFN-beta plasmid DNA delivery or when AAV1 was used as the vector. The experiments demonstrate that gene-based delivery provides sustained levels of IFN-beta compared with bolus protein injection and that Mx1 RNA and IP-10 can be used to monitor biologically active circulating plasma MuIFN-beta protein in mice.
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Base de dados:
MEDLINE
Assunto principal:
Interferon beta
/
Técnicas de Transferência de Genes
/
Proteínas de Ligação ao GTP
/
Quimiocinas CXC
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article