Fig. 10
From: The use of RNA-based treatments in the field of cancer immunotherapy
Inflammatory Reactions to Artificial mRNA. In vitro transcribed (IVT) mRNA is identified by a variety of endosomal innate immune receptors, including Toll-like receptors 3, 7, and 8 (TLR3, TLR7, TLR8), as well as cytoplasmic innate immune receptors like protein kinase RNA-activated (PKR), retinoic acid-inducible gene I protein (RIG-I), melanoma differentiation-associated protein 5 (MDA5), and 2′–5′-oligoadenylate synthase (OAS). These pathways signal to produce inflammation connected with type 1 interferon (IFN), tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-12, and the initiation of various transcriptional programs. Collectively, these elements generate a pro-inflammatory environment conducive to triggering specific immune responses. Furthermore, downstream consequences such as eukaryotic translation initiation factor 2α (eIF2α) phosphorylation-induced translation slowdown, increased RNA degradation due to ribonuclease L (RNASEL) overexpression, and self-amplifying mRNA replication inhibition are significant for the pharmacokinetics and pharmacodynamics of IVT mRNA. Reprinted from [51] with permission from Springer Nature