Gene therapy for cardiovascular diseases : Development of newvector and evaluation of clinical strategy

为了发展心血管疾病的基因治疗，我们重点研究了hvj -脂质体方法作为一种高效、安全的基因传递系统。我们报道了hvj -脂质体方法具有低细胞毒性，是一种适合将基因或寡核苷酸转染到血管和心脏的系统。我们利用这个系统开发了治疗心血管疾病的新策略。我们展示了基因修饰的移植心肌细胞治疗的可能性，并报道了通过冠状动脉转染NFkB诱饵寡核苷酸进入心脏可对缺血性心脏病产生有益的反应。此外，我们报道了基因治疗心脏移植后血管病变的可能性。对于血管疾病，我们使用hvj -脂质体方法研究了转染P21基因、AP-1诱饵、前列腺素基因或NFkB诱饵对血管成形术后再狭窄的影响。我们还报道了抗载脂蛋白(a)的溶酶对动脉粥样硬化的作用。基于这些结果，我们已经进行了使用E2F诱饵寡核苷酸治疗血管成形术后再狭窄的临床试验，现在我们正在计划使用NFkB诱饵治疗再狭窄。为了提高这些策略的效果，我们正在研究hvj -脂质体系统的应用。

To develop gene therapy for cardiovascular diseases, we focused on HVJ-liposome method as an efficient and safe gene delivery system. We reported that HVJ-liposome method has low cytotoxicity and is a suitable system for transfection of gene or oligonucleotides into vessels and hearts.We developed new strategies as treatments of cardiovascular diseases using this system. We showed the possibility of the therapy with gene modified grafted myocytes, and also reported that transfection of NFkB decoy oligonucleotides into hearts via coronary artery resulted in beneficial response to ischemic heart disease. Moreover, we reported the possibility of gene therapy for angiopathy after heart transplantation.For vessel diseases, we showed the effect of transfection of P21 gene, AP-1 decoy, prostacyclin gene, or NFkB decoy on restenosis after angioplasty, using HVJ-liposome method. Also we reported the usefulness of rybozyme against apolipoprotein (a) for atherosclerosis.Based on these results, we have already performed a clinical trial for restenosis after angioplasty using E2F decoy oligonucleotides, and now we are planning a new treatment for restenosis using NFkB decoy. To enhance the effects of these strategies, we are studying about the application of HVJ-liposome system now.