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Updated: May 9, 2026

MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
MicroRNA-145 regulates oncolytic herpes simplex virus-1 for selective killing of human non-small cell lung cancer
Jhy-Ming Li1, Kuo-Chin Kao, Li-Fu Li
1Department of Thoracic Medicine, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kweishan, 333 Taoyuan, Taiwan.
Background:
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide, and novel treatment modalities to improve the prognosis of patients with advanced disease are highly desirable. Oncolytic virotherapy is a promising approach for the treatment of advanced NSCLC. MicroRNAs (miRNAs) may be a factor in the regulation of tumor-specific viral replication. The purpose of this study was to investigate whether miRNA-145 regulated oncolytic herpes simplex virus-1 (HSV-1) can selectively kill NSCLC cells with reduced collateral damage to normal cells.
Methods:
We incorporated 4 copies of miRNA-145 target sequences into the 3'-untranslated region of an HSV-1 essential viral gene, ICP27, to create AP27i145 amplicon viruses and tested their target specificity and toxicity on normal cells and lung cancer cells in vitro.
Results:
miRNA-145 expression in normal cells was higher than that in NSCLC cells. AP27i145 replication was inversely correlated with the expression of miRNA-145 in infected cells. This oncolytic HSV-1 selectively reduced cell proliferation and prevented the colony formation of NSCLC cells. The combination of radiotherapy and AP27i145 infection was significantly more potent in killing cancer cells than each therapy alone.
Conclusions:
miRNA-145-regulated oncolytic HSV-1 is a promising agent for the treatment of NSCLC.
Insights
A novel oncolytic herpes simplex virus-1 (HSV-1) engineered to target miRNA-145 shows promise for treating non-small cell lung cancer (NSCLC). This modified virus selectively kills NSCLC cells, offering a potential new therapy for this deadly disease.
Area of Science:
- Oncolytic virotherapy
- Molecular oncology
- Gene therapy
Background:
- Non-small cell lung cancer (NSCLC) presents a significant global health challenge, driving the need for innovative treatments.
- Oncolytic virotherapy offers a promising strategy for advanced NSCLC.
- MicroRNAs (miRNAs) play a role in regulating virus replication within tumors.
Purpose of the Study:
- To investigate the potential of miRNA-145-regulated oncolytic herpes simplex virus-1 (HSV-1) for selective NSCLC treatment.
- To assess the virus's ability to target NSCLC cells while minimizing damage to normal cells.
Main Methods:
- Engineered HSV-1 (AP27i145) by incorporating miRNA-145 target sequences into the ICP27 gene.
- Evaluated viral replication, target specificity, and toxicity in normal and NSCLC cells in vitro.
Main Results:
- AP27i145 replication was inversely related to miRNA-145 expression levels.
- The oncolytic HSV-1 demonstrated selective killing of NSCLC cells, inhibiting proliferation and colony formation.
- Combined therapy with radiotherapy and AP27i145 significantly enhanced cancer cell killing.
Conclusions:
- miRNA-145-regulated oncolytic HSV-1 represents a promising therapeutic agent for NSCLC.
- This approach offers targeted cancer cell destruction with potentially reduced side effects.
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