Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010 May-Jun;2(3):232-48. doi: 10.1002/wnan.60.
Despite significant advances in surgical and pharmacological techniques, myocardial infarction (MI) remains the main cause of morbidity in the developed world because no remedy has been found for the regeneration of infarcted myocardium. Once the blood supply to the area in question is interrupted, the inflammatory cascade, among other mechanisms, results in the damaged tissue becoming a scar. The goals of cardiac gene therapy are essentially to minimize damage, to promote regeneration, or some combination thereof. While the vector is, in theory, less important than the gene being delivered, the choice of vector can have a significant impact. Viral therapies can have very high transfection efficiencies, but disadvantages include immunogenicity, retroviral-mediated insertional mutagenesis, and the expense and difficulty of manufacture. For these reasons, researchers have focused on non-viral gene therapy as an alternative. In this review, naked plasmid delivery, or the delivery of complexed plasmids, and cell-mediated gene delivery to the myocardium will be reviewed. Pre-clinical and clinical trials in the cardiac tissue will form the core of the discussion. While unmodified stem cells are sometimes considered therapeutic vectors on the basis of paracrine mechanisms of action basic understanding is limited. Thus, only genetically modified cells will be discussed as cell-mediated gene therapy.
尽管在外科和药理学技术方面取得了重大进展，但心肌梗死（MI）仍然是发达国家发病率的主要原因，因为尚未找到治疗梗死心肌再生的方法。一旦相关区域的血液供应中断，炎症级联反应等机制就会导致受损组织形成疤痕。心脏基因治疗的目标本质上是最小化损伤、促进再生，或两者的某种组合。虽然在理论上，载体比所传递的基因重要性低，但载体的选择会产生重大影响。病毒疗法的转染效率非常高，但缺点包括免疫原性、逆转录病毒介导的插入突变和制造的费用和难度。出于这些原因，研究人员专注于非病毒基因治疗作为替代方法。在这篇综述中，将回顾裸露质粒的传递，或复合物质粒的传递，以及细胞介导的基因向心肌的传递。将以心脏组织中的临床前和临床试验为核心进行讨论。虽然未修饰的干细胞有时会根据旁分泌作用机制被认为是治疗性载体，但基本理解是有限的。因此，只有经过基因修饰的细胞才会被讨论为细胞介导的基因治疗。
