Nanomaterials for mRNA‐based therapeutics: Challenges and opportunities

Abstract

Messenger RNA (mRNA) holds great potential in developing immunotherapy, protein replacement, and genome editing. In general, mRNA does not have the risk of being incorporated into the host genome and does not need to enter the nucleus for transfection, and it can be expressed even in nondividing cells. Therefore, mRNA‐based therapeutics provide a promising strategy for clinical treatment. However, the efficient and safe delivery of mRNA remains a crucial constraint for the clinical application of mRNA therapeutics. Although the stability and tolerability of mRNA can be enhanced by directly retouching the mRNA structure, there is still an urgent need to improve the delivery of mRNA. Recently, significant progress has been made in nanobiotechnology, providing tools for developing mRNA nanocarriers. Nano‐drug delivery system is directly used for loading, protecting, and releasing mRNA in the biological microenvironment and can be used to stimulate the translation of mRNA to develop effective intervention strategies. In the present review, we summarized the concept of emerging nanomaterials for mRNA delivery and the latest progress in enhancing the function of mRNA, primarily focusing on the role of exosomes in mRNA delivery. Moreover, we outlined its clinical applications so far. Finally, the key obstacles of mRNA nanocarriers are emphasized, and promising strategies to overcome these obstacles are proposed. Collectively, nano‐design materials exert functions for specific mRNA applications, provide new perception for next‐generation nanomaterials, and thus revolution of mRNA technology.

Extracellular Vesicles: A New Star for Gene Drug Delivery

“… 182 The above results indicate that EVs are superior carriers for the delivery of mRNA because they can prevent the mRNA from sensitive enzymatic degradation in the circulation, thus achieving a high stability after administration. 183 …”

Development of polypeptide-based materials toward messenger RNA delivery

“…The long-term storage of mRNA therapeutic agents and their distribution in areas with limited infrastructure for cold chain storage can be challenging. 95 Furthermore, ensuring that polypeptide-based mRNA delivery systems are manufactured consistently with a high standard of quality is essential for their successful application in therapeutic settings. The Food and Drug Administration (FDA) requires that manufacturers adhere to current Good Manufacturing Practice (cGMP) regulations, which outline specific guidelines for the manufacturing, testing, and quality control of drugs and medical devices.…”

Targeted therapy using engineered extracellular vesicles: principles and strategies for membrane modification

“…mRNAs also possess a remarkable potential for therapy development [ 96 ]. However, mRNA delivery is difficult due to its large size [ 97 ]. Even so, several studies proved the efficiency of EV-delivered mRNA in disease treatment.…”