Gene therapy for new bone formation using adeno-associated viral bone morphogenetic protein-2 vectors.
Gene Ther
; 10(16): 1345-53, 2003 Aug.
Article
en En
| MEDLINE
| ID: mdl-12883531
ABSTRACT
Previous reports have suggested that bone morphogenetic protein (BMP) gene therapy could be applied for in vivo bone regeneration. However, these studies were conducted either using immunodeficient animals because of immunogenicity of adenovirus vectors, or using ex vivo gene transfer technique, which is much more difficult to handle. Adeno-associated virus (AAV) is a replication-defective virus without any association with immunogenicity and human disease. This study was conducted to investigate whether orthotopic new bone formation could be induced by in vivo gene therapy using AAV-based BMP2 vectors. To test the feasibility of this approach, we constructed an AAV vector carrying human BMP2 gene. Mouse myoblast cells (C2C12) transduced with this vector could produce and secrete biologically active BMP2 protein and induce osteogenic activity, which was confirmed by ELISA and alkaline phosphatase activity assay. For in vivo study, AAV-BMP2 vectors were directly injected into the hindlimb muscle of immunocompetent Sprague-Dawley rats. Significant new bone under X-ray films could be detected as early as 3 weeks postinjection. The ossification tissue was further examined by histological and immunohistochemical analysis. This study is, to our knowledge, the first to establish the feasibility of AAV-based BMP2 gene therapy for endochondral ossification in immunocompetent animals.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción Genética
/
Regeneración Ósea
/
Terapia Genética
/
Factor de Crecimiento Transformador beta
/
Dependovirus
/
Proteínas Morfogenéticas Óseas
/
Vectores Genéticos
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Hong Kong