Mechanisms of exRNA Trafficking

项目负责人：Stephen Gould 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， 不断增长的生物系统。exRNA的细胞间运输在人类免疫系统中起着重要作用 健康和疾病，以及用于疾病检测、监测和治疗的exRNA介导的系统， 目前尚未开发的潜力。然而，细胞用来产生 人们对exRNA知之甚少，对exRNA的作用机制几乎一无所知 被人体细胞吸收。这一提议将促进我们对exRNA生物发生机制的理解， 使用多形性胶质母细胞瘤（GBM）模型系统进行摄取，该模型系统集中于通过以下方式产生exRNA： GBM细胞及其被周围的体细胞类型如星形胶质细胞、小胶质细胞和脑细胞摄取 内皮细胞这一提案的成功完成将有助于了解 细胞间RNA运输，测试这些机制的范围和局限性，并产生技术 用于人类和啮齿动物细胞系统中exRNA的工程化生产和摄取。

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.