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

重症新冠肺炎的特点是髓系细胞明显改变，包括骨髓生成和炎性吞噬细胞极化倾向于I型干扰素免疫。到目前为止，对这些观察结果的机械理解有限，阻碍了对这些知识的翻译。这个项目将在我们成功的原始工作计划的基础上，通过探索抗病毒lncRNA和ADAR以及APOBEC RNA编辑在新冠肺炎期间肺泡和外周髓系免疫中的作用来扩展我们的原工作计划。除了对影响新冠肺炎过程的调控核糖核酸电路和核糖核酸编辑事件提供有价值的见解外，我们还将为使用细胞穿透反义核糖核酸抑制剂进行靶向药物干预提供概念验证。我们的项目建立在强大的生物化学专业知识、scRNAseq资源和CRC内可用的患者样本收集的基础上，以提供对新冠肺炎骨髓细胞免疫的更好了解，并为治疗干预开辟新的途径。

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.