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Review
. 2015 Aug:23:25-31.
doi: 10.1016/j.coph.2015.05.004. Epub 2015 May 25.

Targeting microRNAs for immunomodulation

Lukas T Jeker  1 , Romina Marone  2
Affiliations
Review

Targeting microRNAs for immunomodulation

Lukas T Jeker et al. Curr Opin Pharmacol. 2015 Aug.

Abstract

microRNAs (miRNA) are small regulatory RNAs exerting pleiotropic functions in virtually any immune cell-type. Dozens of miRNAs with a known function in the immune system constitute interesting drug targets for immunomodulation. Chemical modifications of nucleic acid-based miRNA mimics and inhibitors largely solved instability issues but delivery to immune cells remains a major challenge. However, recent success targeting the acidic tumor microenvironment is very promising for inflammatory diseases. Moreover, small molecules are being explored as an interesting alternative. Although RNA is often considered 'undruggable' by small molecules recent progress modulating miRNA function through small molecules is encouraging. Computational approaches even allow predictions about specific small molecule/RNA interactions. Finally, recent clinical success demonstrates that drugs targeting RNAs work in humans.

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Figures

Figure 1
Figure 1. Pharmacologic intervention strategies to modulate miRNA biogenesis and function
miRNAs are transcribed by polymerase II into primary miRNAs (pri-miRNA) which are processed into precursor miRNAs (pre-miRNA) by Drosha/Dgcr8. After export to the cytoplasm where further processing occurs through Dicer the mature miRNA is loaded onto Argonaute (Ago) in a multiprotein complex termed RNA induced silencing complex (RISC). The multi-step generation of canonical miRNAs allows modulation of miRNA expression using different approaches to interfere with specific steps of miRNA biogenesis.
  1. 1)

    Small molecule inhibitor of transcription [44]

  2. 2)

    Small molecule pri-miRNA processing inhibitor [48]

  3. 3)

    pre-miRNA processing inhibitor: small molecule or looptomir [39]

  4. 4)

    Small molecule targeting the processing of pre-miRNA-21 by Dicer [47]

  5. 5)

    Inhibitors of mature miRNA: Antisense oligonucleotides; miRNA “sponges”; antagomir; seed targeting LNA-modified antimiRs [28]

  6. 6)

    Delivery of artificial miRNA mimic

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References

    1. Gashaw I, Ellinghaus P, Sommer A, Asadullah K. What makes a good drug target? Drug Discov Today. 2011;16(23-24):1037–1043. - PubMed
    1. Olive V, Minella AC, He L. Outside the coding genome, mammalian micrornas confer structural and functional complexity. Sci Signal. 2015;8(368):re2. - PMC - PubMed
    1. Farh KK, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, Shoresh N, Whitton H, Ryan RJ, Shishkin AA, Hatan M, et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature. 2015;518(7539):337–343. - PMC - PubMed

    1. Ha M, Kim VN. Regulation of microrna biogenesis. Nat Rev Mol Cell Biol. 2014;15(8):509–524. Up-to-date detailed review of miRNA biogenesis.

    1. Vidigal JA, Ventura A. The biological functions of mirnas: Lessons from in vivo studies. Trends Cell Biol. 2015;25(3):137–147. Balanced review of how miRNAs function in vivo. Summarizes and clearly explains many important concepts of miRNA biology.

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