Stead Family Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA.
Genes (Basel). 2020 Mar 26;11(4):351. doi: 10.3390/genes11040351.
Extracellular vesicles (EVs) are a class of naturally occurring secreted cellular bodies that are involved in long distance cell-to-cell communication. Proteins, lipids, mRNA, and miRNA can be packaged into these vesicles and released from the cell. This information is then delivered to target cells. Since EVs are naturally adapted molecular messengers, they have emerged as an innovative, inexpensive, and robust method to deliver therapeutic cargo in vitro and in vivo. Well-differentiated primary cultures of human airway epithelial cells (HAE) are refractory to standard transfection techniques. Indeed, common strategies used to overexpress or knockdown gene expression in immortalized cell lines simply have no detectable effect in HAE. Here we use EVs to efficiently deliver siRNA or protein to HAE. Furthermore, EVs can deliver CFTR protein to cystic fibrosis donor cells and functionally correct the Cl channel defect in vitro. EV-mediated delivery of siRNA or proteins to HAE provides a powerful genetic tool in a model system that closely recapitulates the in vivo airways.
细胞外囊泡（EVs）是一类天然存在的分泌细胞体，参与长距离细胞间通讯。蛋白质、脂质、mRNA 和 miRNA 可以被包装到这些囊泡中，并从细胞中释放出来。然后，这些信息被递送到靶细胞。由于 EVs 是天然适应的分子信使，它们已成为一种创新的、廉价的、稳健的方法，可在体外和体内递送治疗性货物。分化良好的人呼吸道上皮细胞（HAE）原代培养物对标准转染技术具有抗性。事实上，用于在永生化细胞系中过表达或敲低基因表达的常见策略在 HAE 中根本没有可检测到的效果。在这里，我们使用 EVs 有效地将 siRNA 或蛋白质递送到 HAE。此外，EVs 可以将 CFTR 蛋白递送到囊性纤维化供体细胞，并在体外功能性纠正 Cl 通道缺陷。EV 介导的 siRNA 或蛋白质向 HAE 的递送至一种模型系统提供了强大的遗传工具，该模型系统紧密模拟了体内气道。
