Intra-articular electrotransfer of plasmid encoding soluble TNF receptor variants in normal and arthritic mice.
J Gene Med
; 9(11): 986-93, 2007 Nov.
Article
en En
| MEDLINE
| ID: mdl-17912759
BACKGROUND: Anti-inflammatory gene therapy is promising in inflammatory diseases such as rheumatoid arthritis (RA). We have previously demonstrated that intra-muscular (i.m.) electrotransfer (ET) of plasmids encoding three different human tumor necrosis factor-alpha-soluble receptor I variants (hTNFR-Is) exert protective effects in an experimental RA model. However, such a systemic approach could be responsible for side effects. The present study aimed at performing an intra-articular (i.a.) gene therapy by electrotransfer using the hTNFR-Is plasmids. METHODS AND RESULTS: We evaluated targeting of mice joints by CCD optical imaging after i.a. ET of a luciferase-encoding plasmid and we showed that ET led to strongly increased transgene expression in a plasmid dose-dependent manner. Moreover, articular and seric hTNFR-Is was detectable for 2 weeks. As expected, systemic hTNFR-Is rates were lower after i.a. ET than after i.m. ET. A longer protein secretion could be achieved with several i.a. ETs. Also, we observed that hTNFR-Is expression within arthritic joints was slightly higher than in normal joints. CONCLUSIONS: In collagen-induced arthritis (CIA), a mouse model for RA, we demonstrated that hTNFR-Is/mIgG1-encoding plasmid i.a. ET decreased joint destruction in the ankles. In conclusion, our results suggest that local TNFR-Is gene therapy may play a role in decreasing joint destruction in CIA.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plásmidos
/
Artritis Experimental
/
Terapia Genética
/
Sistemas de Liberación de Medicamentos
/
Electroporación
/
Receptores Tipo I de Factores de Necrosis Tumoral
/
Inflamación
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Gene Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Reino Unido