Efficient, cardiac-specific adenoviral gene transfer in rat heart by isolated retrograde perfusion in vivo.
Gene Ther
; 12(12): 958-64, 2005 Jun.
Article
em En
| MEDLINE
| ID: mdl-15789062
ABSTRACT
While a number of virus-based delivery schemes have been developed for myocardial gene transfer, no technique has proven capable of modifying a majority of cardiac myocytes rapidly and homogeneously in the in vivo rat model, and most schemes result in significant infection of the liver and other organs. However, adenoviral delivery to the excised heart during retrograde perfusion can produce 67-92% efficient gene transfer. In this study, we adapt this isolation/perfusion scheme to the heart in vivo. We isolated the heart in vivo by simultaneously clamping all vessels to/from the heart. The heart was then continuously retrograde perfused through a catheter positioned in the aortic root. A second catheter in the right ventricle provided a path for efflux. After perfusing the heart for 7.5 min with calcium-free Tyrode solution followed by 90 s no-flow viral exposure (AdV.cmv.LacZ; 10(12) viral particles/ml), gene transfer efficiency was 60% compared to 5% by a conventional cross-clamp technique. Infection of peripheral organs was dramatically reduced. Given the prevalence of the rat in so many models of heart disease, this enhancement of infection represents an advancement in viral-based delivery of exogenous genes to heart for the study of gene therapy in vivo.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Adenoviridae
/
Vetores Genéticos
/
Miocárdio
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Gene Ther
Ano de publicação:
2005
Tipo de documento:
Article