Self-modulating therapeutic platform using engineered miRNA-responsive oligonucleotides
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.
Authors
- Namseok Lee (ORCID: https://orcid.org/0000-0002-3291-6561)
- Junhyeok Yoon (ORCID: https://orcid.org/0000-0002-0340-2836)
- JinA Lim
- Kyunghoon Hur (ORCID: https://orcid.org/0009-0001-8808-0812)
- Ryeongeun Cho (ORCID: https://orcid.org/0000-0002-0005-4864)
- Doyeong Ku (ORCID: https://orcid.org/0000-0001-6037-0001)
- Jong‐Eun Park (ORCID: https://orcid.org/0000-0003-0718-3463)
- Hyun Gyu Park (ORCID: https://orcid.org/0000-0001-9978-3890)
- Yoosik Kim (ORCID: https://orcid.org/0000-0003-3064-4643)
- Luke P. Lee (ORCID: https://orcid.org/0000-0002-1436-4054)
- Junshik Hong (ORCID: https://orcid.org/0000-0002-7829-397X)
- Jayeon Song
- Hansol Kim
- Sun‐Joon Min (ORCID: https://orcid.org/0000-0003-0867-4416)
- Jun Liu (ORCID: https://orcid.org/0000-0001-8300-8646)
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Seoul National University (KR)
- Korea Advanced Institute of Science and Technology (KR)
- Sungkyunkwan University (KR)
- University of California, Berkeley (US)
Publication Details
- Journal
- Nano Convergence
- Published
- 2025-06-30
- DOI
- https://doi.org/10.1186/s40580-025-00499-w
- Citations
- 1
- Primary Topic
- Advanced biosensing and bioanalysis techniques
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- National Research Foundation
- National Research Foundation of Korea
- Ministry of Science and ICT, South Korea
- Samsung