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Synthetic short mRNA prevents metastasis via innate-adaptive immunity

Author

Listed:
  • Hikaru Hayashi

    (3-1-1 Asahi
    3-1-1 Asahi)

  • Sayaka Seki

    (3-1-1 Asahi)

  • Takeshi Tomita

    (3-1-1 Asahi
    3-1-1 Asahi)

  • Masayoshi Kato

    (3-1-1 Asahi
    3-1-1 Asahi)

  • Norihiro Ashihara

    (3-1-1 Asahi)

  • Tokuhiro Chano

    (Seta Tsukinowa-cho)

  • Hideki Sanjo

    (3-1-1 Asahi)

  • Miwa Kawade

    (1-1 Yanagido)

  • Chenhui Yan

    (3-1-1 Asahi)

  • Hiroki Sakai

    (3-1-1 Asahi
    3-1-1 Asahi)

  • Hidenori Tomida

    (3-1-1 Asahi
    3-1-1 Asahi)

  • Miyuki Tanaka

    (3-1-1 Asahi)

  • Mai Iwaya

    (3-1-1 Asahi)

  • Shinsuke Taki

    (3-1-1 Asahi)

  • Yozo Nakazawa

    (3-1-1 Asahi)

  • Yuji Soejima

    (3-1-1 Asahi)

  • Yoshihito Ueno

    (1-1 Yanagido
    1-1 Yanagido)

  • Sachie Hiratsuka

    (3-1-1 Asahi
    3-1-1 Asahi)

Abstract

Although most cancer deaths are caused by metastasis, there are no effective therapeutic approaches. This study describes the efficacy of a short synthetic mRNA (s-mRNA) designed by the sequence of non-vesicular extracellular IL1β-mRNA found in the pre-metastatic lung of tumor-bearing mice. The administration of s-mRNA inhibits murine lung metastasis by inducing the innate and adaptive immune systems. s-mRNA binds to ZC3H12D, an RNA-binding protein on natural killer cells and cytotoxic T lymphocytes. The ZC3H12D-s-mRNA complex translocated to the nucleus without being involved in translation. This process induces cytolytic activity and cell death in cancer cells without inducing a cytokine storm, and immune cells retain their antitumor activity. Although the antitumor activity of cytotoxic lymphocytes declines as the disease progresses in cancer patients, s-mRNA induces sustained high killing capacities of natural killer cells and cytotoxic T lymphocytes from colon cancer patients. Therefore, s-mRNA could be a breakthrough solution to prevent metastasis.

Suggested Citation

  • Hikaru Hayashi & Sayaka Seki & Takeshi Tomita & Masayoshi Kato & Norihiro Ashihara & Tokuhiro Chano & Hideki Sanjo & Miwa Kawade & Chenhui Yan & Hiroki Sakai & Hidenori Tomida & Miyuki Tanaka & Mai Iw, 2025. "Synthetic short mRNA prevents metastasis via innate-adaptive immunity," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57123-y
    DOI: 10.1038/s41467-025-57123-y
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