Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Gene Ther. 2012 Jun;19(6):670-7. doi: 10.1038/gt.2012.3. Epub 2012 Feb 2.
Several clinical trials are evaluating gene transfer as a therapeutic approach to treat cardiac diseases. Although it has just started on the path to clinical application, recent advances in gene delivery technologies with increasing knowledge of underlying mechanisms raise great expectations for the cardiac gene therapy. Although in vivo experiments using small animals provide the therapeutic potential of gene transfer, there exist many fundamental differences between the small animal and the human hearts. Before applying the therapy to clinical patients, large animal studies are a prerequisite to validate the efficacy in an animal model more relevant to the human heart. Several key factors including vector type, injected dose, delivery method and targeted cardiac disease are all important factors that determine the therapeutic efficacy. Selecting the most optimal combination of these factors is essential for successful gene therapy. In addition to the efficacy, safety profiles need to be addressed as well. In this regard, large animal studies are best suited for comprehensive evaluation at the preclinical stages of therapeutic development to ensure safe and effective gene transfer. As the cardiac gene therapy expands its potential, large animal studies will become more important to bridge the bench side knowledge to the clinical arena.
目前有几项临床试验正在评估基因转移作为治疗心脏疾病的一种方法。虽然它刚刚开始在通往临床应用的道路上，但基因传递技术的最新进展以及对潜在机制的深入了解，为心脏基因治疗带来了巨大的期望。虽然使用小动物的体内实验提供了基因转移的治疗潜力，但小动物和人类心脏之间存在许多基本差异。在将该疗法应用于临床患者之前，大型动物研究是验证更符合人类心脏的动物模型中治疗效果的前提。载体类型、注射剂量、传递方法和靶向心脏疾病等几个关键因素都是决定治疗效果的重要因素。选择这些因素的最佳组合对于成功的基因治疗至关重要。除了疗效外，还需要解决安全性问题。在这方面，大型动物研究最适合在治疗开发的临床前阶段进行全面评估，以确保安全有效的基因传递。随着心脏基因治疗的发展，大型动物研究将变得更加重要，以将基础研究知识转化为临床应用。
