Red Blood Cells could protect miRNAs from degradation or loss thanks to Argonaute 2 binding

Red blood cells (RBCs) have long been considered nucleic acid-free due to their lack of a nucleus. However, recent findings have challenged this view, revealing that RBCs can serve as reservoirs for microRNAs (miRNAs) in the circulation. In this study, we examined the miRNA content and stability in both native and engineered RBCs. Our results demonstrate that RBCs are not only rich in miRNAs but also capable of maintaining miRNA stability under physiological conditions. Interestingly, we observed that this stability persists even after RBCs are subjected to hypotonic dialysis, a common method used in RBC engineering. This suggests that the miRNAs are not merely residual but are retained and protected within the cell. One likely contributor to this stability is the RNA-binding protein Ago2, which is known to associate with miRNAs and appears to play a role in preserving them in RBCs. These findings indicate that RBCs may have potential as natural carriers for RNA molecules. Moreover, beyond their traditional role in oxygen transport, RBCs could be repurposed for therapeutic RNA delivery. This opens up promising avenues for innovations in transfusion medicine and advanced RNA-based therapies, positioning RBCs as a novel platform for clinical applications.