Red blood cells could protect miRNAs from degradation or loss thanks to Argonaute 2 binding

TL;DR

Red blood cells can carry and protect miRNAs due to their binding with Ago2, making them potential tools for RNA-based therapies.

Contribution

The study reveals that Ago2 binding in RBCs protects miRNAs from degradation, enabling their use as RNA delivery vehicles.

Findings

RBCs are rich in miRNAs that remain stable under physiological conditions due to Ago2 binding.

Engineered RBCs retain miRNA stability even after hypotonic dialysis.

miRNA-Ago2 complexes in RBCs are biologically active and prevent miRNA release or degradation.

Abstract

Red blood cells (RBCs) have emerged as reservoirs of microRNAs (miRNAs) in the circulatory system, challenging the traditional view of their nucleic acid absence. This study investigates the miRNA profiles and stability of both native and engineered RBCs. We demonstrate that RBCs are rich in miRNAs, which remain stable under physiological conditions, likely due to their association with Ago2, a key RNA‐binding protein. The stability and retention of miRNAs persist even after hypotonic dialysis used for RBC engineering. These findings underline the potential of RBCs as miRNA carriers for therapeutic applications and as a foundation for RNA‐based delivery systems. Such advancements could redefine their role in transfusion medicine and advanced RNA therapies.

The present work investigates the presence and the stability of miRNAs into RBCs, both native and engineered. The observed stability is due to the Ago2 bound resulting in minimal RISC. Indeed, if the miRNA‐Ago2 complex is present, miRNAs are protected from release or degradation and they are biologically active. Thus, RBCs can act as miRNA carriers for RNA‐based delivery systems.

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