Therapeutic circRNA aptamer alleviates PKR-associated osteoarthritis

Osteoarthritis(OA) is characterized as an inflammation-related disease. Recent studies have identified pattern recognition receptors (PRRs) as key regulators in auto-inflammatory diseases. Protein kinase R (PKR) is a key member of PRRs in vertebrates that recognizes long double-stranded RNAs (dsRNAs) produced from viruses or aberrant cellular dsRNAs. We found out that a general consistency with previous reports that aberrant PKR activation was associated with the OA pathogenesis upon dsRNA stress rather than other stimulations[12], but the role of PKR in the mouse model of OA has not been specified. we selected chondrocytes as the primary target cells to examine the potential application of ds-cRNA(circCAMSAP1 and EPIC) aptamers in OA.And ds-cRNAs delivery showed minimized inflammatory response, high efficacy, safety and beneficial effects on OA phenotypes. Overall design: To make sure IVT circCAMSAP1 contain short dsRNA region, we perform circSHAPE-MaP of IVT circCAMSAP1.