Development of an ultrasound-responsive and mannose-modified gene carrier for DNA vaccine therapy.
Development of an ultrasound-responsive and mannose-modified gene carrier for DNA vaccine therapy.
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DOI：
10.1016/j.biomaterials.2010.06.058
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发表时间：
2010-10
期刊：
影响因子：
14
通讯作者：
K. Un;S. Kawakami;R. Suzuki;K. Maruyama;F. Yamashita;M. Hashida
中科院分区：
文献类型：
--
作者：
K. Un;S. Kawakami;R. Suzuki;K. Maruyama;F. Yamashita;M. Hashida
为了通过基因治疗获得足够的治疗效果，必须开发基因递送系统以选择性地和有效地将目的基因转移到靶细胞中。在这里，我们成功地开发了基因转染方法，使用超声（US）响应和甘露糖修饰的基因载体，命名为Man-PEG 2000气泡lipoplexes。与传统的甘露糖修饰载体脂质体转染方法相比，这种使用Man-PEG 2000泡脂质体复合物和US暴露的转染方法能够在体内选择性地在抗原呈递细胞（APC）中高出约500 - 800倍的基因表达。这种增强的基因表达是由于核酸向靶器官的递送效率的提高，以及US暴露后核酸向细胞质中的引入效率的提高。此外，通过将该方法应用于使用卵清蛋白（OVA）表达质粒DNA（pDNA）的DNA疫苗治疗，证明了高的抗肿瘤效果。该系统可广泛应用于以APCs为靶细胞的疫苗治疗和抗炎治疗等领域，为克服非病毒载体基因导入的主要障碍--载体细胞质导入效率低的问题，建立新的体内基因导入方法提供了新的思路。
Development of a gene delivery system to transfer the gene of interest selectively and efficiently into targeted cells is essential for achievement of sufficient therapeutic effects by gene therapy. Here, we succeeded in developing the gene transfection method using ultrasound (US)-responsive and mannose-modified gene carriers, named Man-PEG2000bubble lipoplexes. Compared with the conventional lipofection method using mannose-modified carriers, this transfection method using Man-PEG2000bubble lipoplexes and US exposure enabled approximately 500∼800-fold higher gene expressions in the antigen presenting cells (APCs) selectively in vivo. This enhanced gene expression was contributed by the improvement of delivering efficiency of nucleic acids to the targeted organs, and by the increase of introducing efficiency of nucleic acids into the cytoplasm followed by US exposure. Moreover, high anti-tumor effects were demonstrated by applying this method to DNA vaccine therapy using ovalbumin (OVA)-expressing plasmid DNA (pDNA). This US-responsive and cell-specific gene delivery system can be widely applied to medical treatments such as vaccine therapy and anti-inflammation therapy, which its targeted cells are APCs, and our findings may help in establishing innovative methods for in-vivo gene delivery to overcome the poor introducing efficiency of carriers into cytoplasm which the major obstacle associated with gene delivery by non-viral carriers.