Mechanisms of exRNA Trafficking

项目负责人：斯蒂芬·古尔德 正在检测功能性细胞外 RNA (exRNA) 的生物发生和细胞间转移 不断增加的生物系统。 exRNA的细胞间运输在人类中发挥着重要作用 健康与疾病，以及用于疾病检测、监测和治疗的 exRNA 介导的系统具有 高但目前尚未开发的潜力。然而，细胞用来产生的分子机制 人们对 exRNA 知之甚少，而且对 exRNA 的机制几乎一无所知 被人体细胞吸收。该提案将增进我们对 exRNA 生物发生和机制的理解 使用多形性胶质母细胞瘤 (GBM) 模型系统进行摄取，该系统专注于通过以下方式产生 exRNA GBM 细胞及其被周围体细胞类型（例如星形胶质细胞、小胶质细胞和大脑）的摄取 内皮细胞。该提案的成功完成将阐明以下机制： 细胞间 RNA 运输，测试这些机制的范围和局限性，并生成技术 用于在人类和啮齿动物细胞系统中工程化生产和摄取 exRNA。

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.