Overexpression of vesicular stomatitis virus G protein (VSV-G) elevates the secretion of EVs known as gectosomes, which contain VSV-G. Such vesicles can be engineered to deliver therapeutic macromolecules. We investigated viral glycoproteins from several viruses for their potential in gectosome production and intracellular cargo delivery. Expression of the viral glycoprotein (viral glycoprotein from the Chandipura virus [CNV-G]) from the human neurotropic pathogen Chandipura virus in 293T cells significantly augments the production of CNV-G-containing gectosomes. In comparison with VSV-G gectosomes, CNV-G gectosomes exhibit heightened selectivity toward specific cell types, including primary cells and tumor cell lines. Consistent with the differential tropism between CNV-G and VSV-G gectosomes, cellular entry of CNV-G gectosome is independent of the Low-density lipoprotein receptor, which is essential for VSV-G entry, and shows varying sensitivity to pharmacological modulators. CNV-G gectosomes efficiently deliver diverse intracellular cargos for genomic modification or responses to stimuli and in the brain of mice utilizing a split GFP and chemical-induced dimerization system. Pharmacokinetics and biodistribution analyses support CNV-G gectosomes as a versatile platform for delivering macromolecular therapeutics intracellularly.

中文翻译：

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金迪普拉病毒糖蛋白 (CNV-G) 促进 Gectosome 生成并实现细胞内治疗药物的传递


水疱性口炎病毒 G 蛋白 (VSV-G) 的过度表达会增加称为囊泡体的 EV 的分泌，其中含有 VSV-G。此类囊泡可被改造以递送治疗性大分子。我们研究了几种病毒的病毒糖蛋白在卵胞体生产和细胞内货物运输中的潜力。来自人类嗜神经病原体金迪普拉病毒的病毒糖蛋白（来自金迪普拉病毒 [CNV-G] 的病毒糖蛋白）在 293T 细胞中的表达显着增加了含有 CNV-G 的果糖体的产生。与 VSV-G 基因体相比，CNV-G 基因体对特定细胞类型（包括原代细胞和肿瘤细胞系）表现出更高的选择性。与 CNV-G 和 VSV-G 基因体之间的差异向性一致，CNV-G 基因体的细胞进入独立于低密度脂蛋白受体，而低密度脂蛋白受体对于 VSV-G 进入至关重要，并且对药理调节剂表现出不同的敏感性。 CNV-G 基因胞体利用分裂 GFP 和化学诱导的二聚化系统，有效地在小鼠大脑中传递多种细胞内货物，用于基因组修饰或对刺激的反应。药代动力学和生物分布分析支持 CNV-G 基因胞体作为在细胞内提供大分子治疗药物的多功能平台。