Current and Future Advancements in miRNA Therapeutics Delivery Systems for Regenerative Medicine

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Silvan Saputra
Reza Yuridian Purwoko
Budi Wiweko
Ivan R. Sini
Nining Handayani

Abstract

MicroRNA (miRNA) therapeutics offer a promising approach to treating complex diseases by modulating gene expression. However, challenges such as instability, poor cellular uptake, off-target effects, and immune responses limit their clinical use. This review synthesizes recent advancements in delivery systems aimed at overcoming these challenges, with a focus on regenerative medicine. A systematic review of the past decade’s literature highlights key delivery platforms, including lipid-based nanoparticles, polymeric carriers, and exosome-based systems. Lipid-based systems, such as liposomes and solid lipid nanoparticles, provide enhanced stability and targeted delivery, particularly in cancer and cardiovascular therapies. Polymeric carriers, like PLGA and chitosan nanoparticles, enable controlled release and improved biocompatibility for long-term applications. Exosome-based delivery systems mimic natural cellular communication, facilitating efficient miRNA transfer with reduced immunogenicity. The review underscores the importance of chemical modifications, endocytosis-enhancing strategies, and stimuli-responsive materials in optimizing therapeutic efficacy. Combining bioengineering advancements with artificial intelligence holds potential to refine delivery systems and expedite clinical translation. Despite these innovations, challenges like scalability, regulatory issues, and manufacturing costs remain barriers to widespread adoption. This study highlights key opportunities and outlines future research directions to establish miRNA therapeutics as a cornerstone in regenerative medicine.

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References

Arafiles, J. V. V., Hirose, H., Akishiba, M., Tsuji, S., Imanishi, M., & Futaki, S. (2020). Stimulating Macropinocytosis for Intracellular Nucleic Acid and Protein Delivery: A Combined Strategy with Membrane-Lytic Peptides To Facilitate Endosomal Escape. Bioconjugate Chemistry, 31(3), 547–553. https://doi.org/10.1021/acs.bioconjchem.0c00064

Badkar, A. V., Gandhi, R. B., Davis, S. P., & LaBarre, M. J. (2021). Subcutaneous Delivery of High-Dose/Volume Biologics: Current Status and Prospect for Future Advancements. Drug Design Development and Therapy, Volume 15, 159–170. https://doi.org/10.2147/dddt.s287323

Bai, Z., Wei, J., Yu, C., Han, X., Qin, X., Zhang, C., Liao, W., Li, L., & Huang, W. (2019).

Non-viral nanocarriers for intracellular delivery of microRNA therapeutics. Journal of Materials Chemistry B, 7(8), 1209–1225. https://doi.org/10.1039/c8tb02946f

Ban, E., Kwon, T., & Kim, A. (2019). Delivery of therapeutic miRNA using polymer-based formulation. Drug Delivery and Translational Research, 9(6), 1043–1056. https://doi.org/10.1007/s13346-019-00645-y

Bejerano, T., Etzion, S., Elyagon, S., Etzion, Y., & Cohen, S. (2018). Nanoparticle Delivery of miRNA-21 Mimic to Cardiac Macrophages Improves Myocardial Remodeling after Myocardial Infarction. Nano Letters, 18(9), 5885–5891. https://doi.org/10.1021/acs.nanolett.8b02578

Carreras-Badosa, G., Maslovskaja, J., Periyasamy, K., Urgard, E., Padari, K., Vaher, H., Tserel, L., Gestin, M., Kisand, K., Arukuusk, P., Lou, C., Langel, Ü., Wengel, J., Pooga, M., & Rebane,