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Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers

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 th...

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Autores principales: Ahn, Hye-Hyun, Carrington, Christine, Hu, Yizong, Liu, Heng-wen, Ng, Christy, Nam, Hwanhee, Park, Andrew, Stace, Catherine, West, Will, Mao, Hai-Quan, Pomper, Martin G., Ullman, Christopher G., Minn, Il
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102550/
https://www.ncbi.nlm.nih.gov/pubmed/33958660
http://dx.doi.org/10.1038/s41598-021-89124-4
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author Ahn, Hye-Hyun
Carrington, Christine
Hu, Yizong
Liu, Heng-wen
Ng, Christy
Nam, Hwanhee
Park, Andrew
Stace, Catherine
West, Will
Mao, Hai-Quan
Pomper, Martin G.
Ullman, Christopher G.
Minn, Il
author_facet Ahn, Hye-Hyun
Carrington, Christine
Hu, Yizong
Liu, Heng-wen
Ng, Christy
Nam, Hwanhee
Park, Andrew
Stace, Catherine
West, Will
Mao, Hai-Quan
Pomper, Martin G.
Ullman, Christopher G.
Minn, Il
author_sort Ahn, Hye-Hyun
collection PubMed
description 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.
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spelling pubmed-81025502021-05-10 Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers Ahn, Hye-Hyun Carrington, Christine Hu, Yizong Liu, Heng-wen Ng, Christy Nam, Hwanhee Park, Andrew Stace, Catherine West, Will Mao, Hai-Quan Pomper, Martin G. Ullman, Christopher G. Minn, Il Sci Rep Article 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. Nature Publishing Group UK 2021-05-06 /pmc/articles/PMC8102550/ /pubmed/33958660 http://dx.doi.org/10.1038/s41598-021-89124-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ahn, Hye-Hyun
Carrington, Christine
Hu, Yizong
Liu, Heng-wen
Ng, Christy
Nam, Hwanhee
Park, Andrew
Stace, Catherine
West, Will
Mao, Hai-Quan
Pomper, Martin G.
Ullman, Christopher G.
Minn, Il
Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers
title Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers
title_full Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers
title_fullStr Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers
title_full_unstemmed Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers
title_short Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers
title_sort nanoparticle-mediated tumor cell expression of mil-12 via systemic gene delivery treats syngeneic models of murine lung cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102550/
https://www.ncbi.nlm.nih.gov/pubmed/33958660
http://dx.doi.org/10.1038/s41598-021-89124-4
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