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

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,...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/028da9e9162b445aa5e23cd58b3acf81
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spelling	oai:doaj.org-article:028da9e9162b445aa5e23cd58b3acf812021-12-02T14:41:56ZNanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers10.1038/s41598-021-89124-42045-2322https://doaj.org/article/028da9e9162b445aa5e23cd58b3acf812021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89124-4https://doaj.org/toc/2045-2322Abstract 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.Hye-Hyun AhnChristine CarringtonYizong HuHeng-wen LiuChristy NgHwanhee NamAndrew ParkCatherine StaceWill WestHai-Quan MaoMartin G. PomperChristopher G. UllmanIl MinnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers
description	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.
format	article
author	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
author_facet	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
author_sort	Hye-Hyun Ahn
title	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_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_sort	nanoparticle-mediated tumor cell expression of mil-12 via systemic gene delivery treats syngeneic models of murine lung cancers
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/028da9e9162b445aa5e23cd58b3acf81
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Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers

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