Mechanisms of exRNA Trafficking

项目负责人：斯蒂芬·古尔德 功能性细胞外RNA(ExRNA)的生物发生和细胞间转移正在被检测到 不断增加的生物系统阵列。外源RNA的细胞间运输在人类中起着重要作用 健康与疾病，以及外源RNA介导的疾病检测、监测和治疗系统具有 潜力很大，但目前尚未开发。然而，细胞用来产生 人们对exRNA的了解很少，而且对exRNA的作用机制几乎一无所知。 被人类细胞摄取。这一建议将促进我们对exRNA生物发生和 利用多形性胶质母细胞瘤(GBM)模型系统摄取，该模型系统侧重于通过 GBM细胞及其周围体细胞类型，如星形胶质细胞、小胶质细胞和脑的摄取 内皮细胞。这项提案的成功完成将有助于揭示 细胞间RNA贩运，测试这些机制的范围和局限性，并产生技术 用于在人类和啮齿动物细胞系统中工程生产和摄取外源RNA。

Project Leader: Stephen Gould The biogenesis and intercellular transfer of functional, extracellular RNA (exRNA) is being detected in an ever-increasing array of biological systems. Intercellular traffic of exRNA plays important roles in human health and disease, and exRNA-mediated systems for disease detection, monitoring, and therapy have a high yet currently untapped potential. However, the molecular mechanisms that cells use to generate exRNAs are only poorly understood, and there is virtually nothing known about the mechanisms of exRNA uptake by human cells. This proposal will advance our mechanistic understanding of exRNA biogenesis and uptake using a glioblastoma multiforme (GBM) model system that focuses on the production of exRNAs by GBM cells, and their uptake by surrounding somatic cell types such as astrocytes, microglia, and brain endothelial cells. The successful completion of this proposal will shed light on the mechanisms of intercellular RNA trafficking, test the scope and limitations of these mechanisms, and generate technologies for the engineered production and uptake of exRNA in human and rodent cell systems.