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  • Review Article
  • Published:

Therapeutic targeting of microRNAs: current status and future challenges

Key Points

  • MicroRNAs (miRNAs) have important roles in many aspects of human diseases, and their targeted inhibition may have substantial therapeutic impact.

  • Inhibition of miRNAs can be achieved through a variety of methods and chemically modified antisense oligonucleotides (anti-miRs) have shown the most prominent effects.

  • Targeted delivery of anti-miRs is crucial to achieve intended therapeutic effects, and further efforts are warranted to develop more efficient delivery systems.

Abstract

MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that have crucial roles in regulating gene expression. Increasing evidence supports a role for miRNAs in many human diseases, including cancer and autoimmune disorders. The function of miRNAs can be efficiently and specifically inhibited by chemically modified antisense oligonucleotides, supporting their potential as targets for the development of novel therapies for several diseases. In this Review we summarize our current knowledge of the design and performance of chemically modified miRNA-targeting antisense oligonucleotides, discuss various in vivo delivery strategies and analyse ongoing challenges to ensure the specificity and efficacy of therapeutic oligonucleotides in vivo. Finally, we review current progress on the clinical development of miRNA-targeting therapeutics.

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Figure 1: Canonical and non-canonical miRNA biogenesis pathways.
Figure 2: miRNA function: three potential mechanisms of miRNA-mediated post-transcriptional gene silencing.
Figure 3: miRNA inhibition strategies.
Figure 4: Chemically modified miRNA-targeting oligonucleotides.

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Acknowledgements

We are grateful to our colleague Dr R. Zhou and members of the Rana laboratory for helpful discussions. We apologize to our colleagues whose work we could not cite owing to space limitations. This work was supported in part by grants from the US National Institutes of Health (to T.M.R).

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Correspondence to Tariq M. Rana.

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Li, Z., Rana, T. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov 13, 622–638 (2014). https://doi.org/10.1038/nrd4359

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