Hepatic-stellate-cell-targeted delivery of PU.1 decoy ODN by Apt-Tan attenuates liver fibrosis in mice
Targeted therapeutics for liver fibrosis (LF) are unavailable. PU.1 is a pioneer transcription factor (TF) that promotes hepatic stellate cell (HSC) activation and LF. PU.1 decoy oligodeoxynucleotides (ODNs) can potentially repress LF by capturing PU.1. In this study, we used Apt-Tan, a hepatic stellate cell (HSC)-internalizing DNA aptamer selected through the cell systematic evolution of ligands by exponential enrichment (Cell-SELEX), and validated the anti-LF effect of a combination of Apt-Tan and PU.1 decoy ODN in mice. Furthermore, intravenous injection of Apt-Tan- PU.1 decoy ODN repressed the expression of PU.1 downstream pro-fibrotic genes such as <i>TIMP1</i>, alleviated liver injury, and reduced extracellular matrix deposition in mice model of LF induced by CCL<sub>4</sub>. Apt-Tan- PU.1 decoy ODN demonstrated anti-fibrosis potential and warranted further investigation.
Authors
- Jiangfeng Wu (ORCID: https://orcid.org/0000-0002-4717-0141)
- Siyuan Wu (ORCID: https://orcid.org/0000-0002-9041-8587)
- Yanqiong Zhang (ORCID: https://orcid.org/0000-0002-9358-111X)
- Yi‐Ran Ni (ORCID: https://orcid.org/0000-0002-4298-3231)
- Botao Li (ORCID: https://orcid.org/0000-0001-5487-9231)
- Xiaojing Wu (ORCID: https://orcid.org/0000-0002-0590-7627)
- Yong Tan
- Ying Wang (ORCID: https://orcid.org/0000-0001-8020-3622)
- Liye Zhang (ORCID: https://orcid.org/0000-0003-2104-6828)
- Lan Ma (ORCID: https://orcid.org/0000-0001-7797-1436)
- Xiaojie Luo
- Yue Sun
Institutions
- China Three Gorges University (CN)
- The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture (CN)
Publication Details
- Journal
- Molecular Therapy — Nucleic Acids
- Published
- 2025-06-16
- DOI
- https://doi.org/10.1016/j.omtn.2025.102607
- Citations
- 2
- Primary Topic
- Liver physiology and pathology
- Type
- article
- Field-Weighted Citation Impact
- 2.64
Funders
- National Natural Science Foundation of China