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

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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.