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<p>Due to a pivotal role in the post-transcriptional regulation of genes implicated in numerous diseases, miRNAs serve as promising disease biomarkers and therapeutic targets. We introduce a new oligonucleotide probe termed miRNA-trigger, which selectively downregulates newly assigned target mRNAs by hijacking specific miRNAs. By engineering the miRNA-trigger to suppress the anti-apoptotic <i>BCL-xL</i> gene, we induce apoptosis selectively in breast cancer cells overexpressing specific miRNAs and further validate its therapeutic efficacy in vivo, by significantly reducing the tumor volume of the xenograft mouse upon its tail-vein injection. This approach establishes a new platform for self-modulating oligonucleotide therapy by redirecting disease-associated miRNAs.</p> Graphical Abstract <p></p>

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Self-modulating therapeutic platform using engineered miRNA-responsive oligonucleotides

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月30日

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  • Doyeong Ku,
  • Hansol Kim,
  • JinA Lim,
  • Jayeon Song,
  • Junhyeok Yoon,
  • Liu Jun,
  • Su-Ji Min,
  • Ryeongeun Cho,
  • Namseok Lee,
  • Kyunghoon Hur,
  • Jong-Eun Park,
  • Luke P. Lee,
  • Junshik Hong,
  • Yoosik Kim,
  • Hyun Gyu Park

摘要

Due to a pivotal role in the post-transcriptional regulation of genes implicated in numerous diseases, miRNAs serve as promising disease biomarkers and therapeutic targets. We introduce a new oligonucleotide probe termed miRNA-trigger, which selectively downregulates newly assigned target mRNAs by hijacking specific miRNAs. By engineering the miRNA-trigger to suppress the anti-apoptotic BCL-xL gene, we induce apoptosis selectively in breast cancer cells overexpressing specific miRNAs and further validate its therapeutic efficacy in vivo, by significantly reducing the tumor volume of the xenograft mouse upon its tail-vein injection. This approach establishes a new platform for self-modulating oligonucleotide therapy by redirecting disease-associated miRNAs.

Graphical Abstract