Harnessing RNA molecules for therapy: advances in design, delivery, and clinical development

Abstract

RNA-based therapeutics have emerged as attractive candidates for clinical applications, offering distinct advantages over conventional small-molecule drugs, which play an important role in the treatment of a variety of diseases. Through specific and rational design, exogenous coding/noncoding RNA therapeutics, including messenger RNA (mRNA), small interfering RNA (siRNA), RNA aptamers, microRNA (miRNA), antisense oligonucleotides (ASOs), short activating RNA (saRNA), RNA aptamers, circular RNA (circRNA), and CRISPR-based therapeutics are increasingly used to modulate the process of diseases at the genetic level. However, insufficient cellular delivery, RNA instability, and complex in vivo biological barriers significantly limit the therapeutic efficacy of RNA therapeutics. Numerous delivery strategies (e.g., nanotechnology, material-based carriers, and structural modification) have been used to overcome these key issues. In this review, the ongoing development and latest advances in RNA therapeutics are thoroughly summarized, focusing on therapeutic mechanisms, delivery challenges, and emerging drug delivery strategies. In particular, the clinical applications and current challenges in translating RNA therapeutics are discussed, highlighting future directions and opportunities to improve clinical efficacy.

Keywords

Drug delivery / RNA therapeutics / Biological barriers / Clinical applications / Translation challenges

Ethical statements

Not applicable.

Author contributions

The authors confirm their contributions to the paper as follows: study conception: He W; writing—original draft: Zou J, He X, Li Z, Song B, Xing X, Yu J; review & editing: He W. All authors reviewed the results and approved the final version of the manuscript.

Data availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Acknowledgments

This study was supported by the National Natural Science Foundation of China (Nos. 82073782 and 82241002).

Conflict of Interest

The authors declare that they have no conflict of interest.

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