Dissecting the role of RNA in host defence and immune-subversion by SARS-CoV-2 (C10*)

剖析 RNA 在 SARS-CoV-2 (C10*) 宿主防御和免疫颠覆中的作用

• 批准号: 405490340
• 金额: --
• 依托单位: Institut für Immunologie
• 依托单位国家: 德国
• 项目类别: CRC/Transregios
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405490340?language=en
• 关键词: Dissecting; role; RNA; host; defence

Severe COVID-19 is marked by significant alterations in the myeloid cell compartment, including myelopoiesis and inflammatory phagocyte polarization towards type I interferon immunity. So far, a limited mechanistic understanding of these observations hampers translation of this knowledge. This project will expand upon our successful original work program by exploring the roles of antiviral lncRNAs and ADAR and APOBEC RNA-editing in alveolar and peripheral myeloid immunity during COVID-19. Besides providing valuable insights into regulatory RNA circuits and RNA editing events affecting the course of COVID-19, we will provide proof-of-concept for targeted pharmacological intervention using cell-penetrating antisense RNA-inhibitors. Our project builds on strong biochemistry expertise, scRNAseq resources and patient sample collections available within the CRC, to provide an improved understanding of myeloid cell immunity in COVID-19 and to open new avenues for therapeutic intervention.

严重的 COVID-19 的特点是骨髓细胞区室发生显着改变，包括骨髓生成和炎症吞噬细胞向 I 型干扰素免疫的极化。到目前为止，对这些观察结果的有限机械理解阻碍了这些知识的转化。该项目将通过探索抗病毒 lncRNA 以及 ADAR 和 APOBEC RNA 编辑在 COVID-19 期间肺泡和外周骨髓免疫中的作用，扩展我们成功的原创工作计划。除了提供有关影响 COVID-19 病程的调控 RNA 回路和 RNA 编辑事件的宝贵见解外，我们还将为使用细胞穿透性反义 RNA 抑制剂进行靶向药理干预提供概念验证。我们的项目建立在 CRC 内强大的生物化学专业知识、scRNAseq 资源和患者样本收集的基础上，以更好地了解 COVID-19 中的骨髓细胞免疫，并为治疗干预开辟新途径。