新型siRNA阳离子脂质体抑制乙肝病毒HBx基因表达

Novel cationic liposome loading siRNA inhibits the expression of hepatitis B virus HBx gene

为解决siRNA药物应用过程中存在的siRNA筛选和体内转运的问题,以乙肝病毒基因HBx为研究对象,通过构建表达目的基因和荧光素酶融合蛋白的双荧光素酶质粒,体外筛选得到有效抑制HBx基因的表达siRNA序列的质粒,并将该siRNA表达质粒装载于PEG化修饰的新型阳离子脂质体中,在细胞和动物水平开展该阳离子脂质体的作用效果研究。结果表明,上述装载siRNA质粒的阳离子脂质体能够在细胞和动物水平有效地抑制乙肝病毒HBx基因的表达,解决了siRNA应用中序列筛选和体内转运的问题。

In order to solve the problem of selection and in vivo delivery problem in siRNA treatment, hepatitis B virus （HBV） HBx gene which could be targeted by siRNA was studied. The siRNA expression plasmid which specific inhibits HBx expression was obtained by in vitro selection via a dual-luciferase plasmid including HBx-Fluc fusion protein expression domain. The selected siRNA expression plasmid was then encapsulated in PEG-modified cationic liposome, which was devoted into pharmacodynamic studies at both cellular and animal level. The results illustrated that the cationic liposome which encapsulated siRNA expression plasmid could effectively inhibit HBx gene expression both in vitro and in vivo.