Gene vectors play a critical role in gene therapy. To achieve efficient transfection, we developed a novel nonvirus cationic liposome (Lipo-Par), which was bound covalently with the cationic polypeptide pardaxin (Par). Interestingly, the Lipo-Pars exhibited highly enhanced gene transfection efficiency in various cell lines compared to that of the non-Par-bonded liposomes (Lipo-Nons). As a result, the internalization and intracellular transport mechanisms of the Lipo-Pars were investigated, and the findings indicated their ability to actively target the endoplasmic reticulum (ER) by moving along the cell cytoskeleton after undergoing caveolin-mediated endocytosis. This intracellular transport process is similar to that of some viruses. It was also found that ER stress and calcium level disturbances can affect the Lipo-Par-mediated expression of certain exogenous genes. A possible, yet non-negligible explanation for the high transfection efficiency of the Lipo-Par is its virus-like intracellular behavior and the intimate relationship between the ER membrane and the nuclear envelope.

中文翻译：

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通过内质网途径有效传递基因的病毒样非病毒阳离子脂质体。

基因载体在基因治疗中起关键作用。为了实现有效的转染，我们开发了一种新型的非病毒阳离子脂质体（Lipo-Par），该脂质体与阳离子多肽pardaxin（Par）共价结合。有趣的是，与非对位键合脂质体（Lipo-Nons）相比，Lipo-Pars在各种细胞系中均表现出高度增强的基因转染效率。结果，研究了Lipo-Pars的内在化和细胞内转运机制，发现表明它们在经历小窝蛋白介导的内吞作用后，通过沿着细胞骨架移动而主动靶向内质网（ER）。这种细胞内转运过程与某些病毒相似。还发现内质网应激和钙水平紊乱可影响Lipo-Par介导的某些外源基因的表达。对于Lipo-Par的高转染效率，可能的但不能忽略的解释是其病毒样细胞内行为以及ER膜与核膜之间的密切关系。