New development of efficient gene transfer into in vivo myocardium and evaluation of cardiac function after the treatment.

点击翻译按钮获取中文摘要

At the end-stage of advanced heart failure, cardiac transplantation is a finally available treatment. In the present study, authors have addressed the development of new strategy using gene therapy, based on our preceding studies, employing TO-2 strain hamsters as human DCM model. We prepared reporter gene (Lac Z) or full-length δ-sargoglycan (SG) gene, both of which were driven by CMV promoter and intramurally administered to the apex of the animals under open-chest surgery. The transcript and transgene analyzed by Northern blotting and Western blotting, respectively, revealed both expressions at 10 to 40 weeks later, indicating the appreciable and long-lasting effect of the rAAV vector. Cell-exclusion analysis of Evans blue staining and δ-SG immunostaining denoted that cardiomyocytes after the efficient expression of δ-SG protein demonstrated normalized cell-permeability. Physiological indices measured in vivo by echocardiography and cardiac catheterization also indicated an improved cardiac performances. Finally, Kaplan-Meier's analysis of the animals distinctly certified an improved survival rate in a group cotransfected by Lac Z and δ-SG gene, compared with another group treated by Lac Z alone. These data have provided the first evidence for the effective gene therapy of advanced heart failure and are expected to be applicable for the treatment in human cases in future.