Autor: |
Hye-Hyun Ahn, Christine Carrington, Yizong Hu, Heng-wen Liu, Christy Ng, Hwanhee Nam, Andrew Park, Catherine Stace, Will West, Hai-Quan Mao, Martin G. Pomper, Christopher G. Ullman, Il Minn |
Jazyk: |
angličtina |
Rok vydání: |
2021 |
Předmět: |
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Zdroj: |
Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
Druh dokumentu: |
article |
ISSN: |
2045-2322 |
DOI: |
10.1038/s41598-021-89124-4 |
Popis: |
Abstract Treatment of cancers in the lung remains a critical challenge in the clinic for which gene therapy could offer valuable options. We describe an effective approach through systemic injection of engineered polymer/DNA nanoparticles that mediate tumor-specific expression of a therapeutic gene, under the control of the cancer-selective progression elevated gene 3 (PEG-3) promoter, to treat tumors in the lungs of diseased mice. A clinically tested, untargeted, polyethylenimine carrier was selected to aid rapid transition to clinical studies, and a CpG-free plasmid backbone and coding sequences were used to reduce inflammation. Intravenous administration of nanoparticles expressing murine single-chain interleukin 12, under the control of PEG-3 promoter, significantly improved the survival of mice in both an orthotopic and a metastatic model of lung cancer with no marked symptoms of systemic toxicity. These outcomes achieved using clinically relevant nanoparticle components raises the promise of translation to human therapy. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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