Kotani Hitoshi, Nakajima Toshihiro, Lai Shoupeng, Morishita Ryuichi, Kaneda Yasufumi
AnGes MG, Inc., 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan.
Curr Gene Ther. 2004 Jun;4(2):183-94. doi: 10.2174/1566523043346471.
Recently promising results of gene therapy clinical trials have been reported for treatment of peripheral vascular and cardiovascular diseases using various angiogenic growth factors and other therapeutic genes. Viral vector and non-viral vector systems were employed in preclinical studies and clinical trials. Adenoviral vector and naked plasmid have been used most in the clinical studies. HVJ (hemagglutinating virus of Japan or Sendai virus)-liposome vector, a hybrid non-viral vector system with fusion of inactivated HVJ virus particle and liposome, has developed and demonstrated high transfection efficiency in preclinical studies of many different disease models, including a wide range of cardiovascular disease models. However, some limitations exist in the HVJ-liposome technology, especially in the scalability of its production. Recently an innovative vector technology, HVJ envelope (HVJ-E) has been developed as a non-viral vector, consisting of HVJ envelope without its viral genome, which is eliminated by a combination of inactivation and purification steps. HVJ-E is able to enclose various molecule entities, including DNA, oligonucleotides, proteins, as single or multiple therapeutic remedies. The therapeutic molecule-included HVJ-E vector can transfect various cell types in animals and humans with high efficiency. In this review, vector technology for cardiovascular disease and the biology of HVJ-E vector technology is discussed.
最近有报道称,使用各种血管生成生长因子和其他治疗性基因治疗外周血管疾病和心血管疾病的基因治疗临床试验取得了令人鼓舞的结果。病毒载体和非病毒载体系统已用于临床前研究和临床试验。腺病毒载体和裸质粒在临床研究中使用最为广泛。HVJ(日本血凝病毒或仙台病毒)-脂质体载体是一种将灭活的HVJ病毒颗粒与脂质体融合的混合非病毒载体系统,在包括多种心血管疾病模型在内的许多不同疾病模型的临床前研究中已得到发展并显示出高转染效率。然而,HVJ-脂质体技术存在一些局限性,尤其是在其生产的可扩展性方面。最近,一种创新的载体技术——HVJ包膜(HVJ-E)已被开发为一种非病毒载体,它由不含病毒基因组的HVJ包膜组成,通过灭活和纯化步骤相结合将病毒基因组去除。HVJ-E能够包裹各种分子实体,包括DNA、寡核苷酸、蛋白质,作为单一或多种治疗药物。包含治疗分子的HVJ-E载体能够高效转染动物和人类的各种细胞类型。在这篇综述中,将讨论用于心血管疾病的载体技术以及HVJ-E载体技术的生物学特性。