2. Academic Validation
  3. Copper-mediated siRNA activation for conditional control of gene expression

Copper-mediated siRNA activation for conditional control of gene expression

  • Bioorg Med Chem Lett. 2024 May 15:104:129738. doi: 10.1016/j.bmcl.2024.129738.
Kunihiko Morihiro 1,  Yasuhiro Tomida 2,  Honami Ando 2,  Akimitsu Okamoto 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. Electronic address: morihiro@chembio.t.u-tokyo.ac.jp.
  • 2 Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
  • 3 Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. Electronic address: okamoto@chembio.t.u-tokyo.ac.jp.
PMID: 38593925 DOI: 10.1016/j.bmcl.2024.129738
Abstract

Copper plays a crucial role in maintaining biological redox balance in living organisms, with elevated levels observed in Cancer cells. Short interfering RNAs (siRNAs) are effective in gene silencing and find applications as both research tools and therapeutic agents. A method to regulate RNA interference using copper is especially advantageous for cancer-specific therapy. We present a chemical approach of selective siRNA activation triggered by intracellular copper ions. We designed and synthesized nucleotides containing copper-responsive moieties, which were incorporated into siRNAs. These copper-responsive siRNAs effectively silenced the target cyclin B1 mRNA in living cells. This pioneering study introduces a novel method for conditionally controlling gene silencing using biologically relevant metal ions in human cells, thereby expanding the repertoire of chemical knockdown tools.

Keywords

Copper; DNA; Nucleic acids; Prodrugs; siRNA.

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