Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy

Xueyan Zhang,1 Ke Men,1 Yuanfa Zhang,1 Rui Zhang,1 Li Yang,1 Xingmei Duan21State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Pharmacy and P...

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Autores principales:	Zhang X, Men K, Zhang Y, Zhang R, Yang L, Duan X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	mRNA gene therapy colon cancer non-viral vector systemic delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f96a93c8e95e43cbae6d657cd631d78a
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spelling	oai:doaj.org-article:f96a93c8e95e43cbae6d657cd631d78a2021-12-02T09:49:00ZLocal and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy1178-2013https://doaj.org/article/f96a93c8e95e43cbae6d657cd631d78a2019-04-01T00:00:00Zhttps://www.dovepress.com/local-and-systemic-delivery-of-mrna-encoding-survivin-t34a-by-lipoplex-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xueyan Zhang,1 Ke Men,1 Yuanfa Zhang,1 Rui Zhang,1 Li Yang,1 Xingmei Duan21State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Pharmacy and Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072, People’s Republic of ChinaBackground: In vitro transcribed (IVT) mRNA has been applied as an alternative therapeutic molecule to plasmid DNA in the field of cancer therapy and biomedical research studies. mRNA-based therapy has demonstrated several advantages over its DNA counterparts. However, its further therapeutic application is largely restricted by delivery method.Methods: In this work, a liposome-protamine lipoplex (CLPP) was prepared to deliver IVT mRNA encoding survivin-T34A gene, forming a novel core-shell structured nanoparticle formulation (CLPP/mSur-T34A).Results: The prepared CLPP/mSur-T34A particle had an average size of 186.1±3.1 nm, displaying high mRNA transfecting and expression efficiency on C26 tumor cells through lipid rafts-mediated endocytosis. CLPP/mSur-T34A mRNA formulation demonstrated obvious therapeutic effects on various models of C26 colon cancer both in vitro and in vivo. Particularly, local and systemic administration of CLPP/mSur-T34A particle exhibited superior antitumor effect regarding its DNA plasmid counterpart with high safety.Conclusion: Our results indicated the high delivery capacity of liposome-protamine lipoplex and further suggested CLPP/mSur-T34A mRNA formulation to be a potential candidate for colon cancer therapy.Keywords: mRNA gene therapy, colon cancer, nonviral vector, systemic deliveryZhang XMen KZhang YZhang RYang LDuan XDove Medical PressarticlemRNA gene therapycolon cancernon-viral vectorsystemic deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 2733-2751 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	mRNA gene therapy colon cancer non-viral vector systemic delivery Medicine (General) R5-920
spellingShingle	mRNA gene therapy colon cancer non-viral vector systemic delivery Medicine (General) R5-920 Zhang X Men K Zhang Y Zhang R Yang L Duan X Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy
description	Xueyan Zhang,1 Ke Men,1 Yuanfa Zhang,1 Rui Zhang,1 Li Yang,1 Xingmei Duan21State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Pharmacy and Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072, People’s Republic of ChinaBackground: In vitro transcribed (IVT) mRNA has been applied as an alternative therapeutic molecule to plasmid DNA in the field of cancer therapy and biomedical research studies. mRNA-based therapy has demonstrated several advantages over its DNA counterparts. However, its further therapeutic application is largely restricted by delivery method.Methods: In this work, a liposome-protamine lipoplex (CLPP) was prepared to deliver IVT mRNA encoding survivin-T34A gene, forming a novel core-shell structured nanoparticle formulation (CLPP/mSur-T34A).Results: The prepared CLPP/mSur-T34A particle had an average size of 186.1±3.1 nm, displaying high mRNA transfecting and expression efficiency on C26 tumor cells through lipid rafts-mediated endocytosis. CLPP/mSur-T34A mRNA formulation demonstrated obvious therapeutic effects on various models of C26 colon cancer both in vitro and in vivo. Particularly, local and systemic administration of CLPP/mSur-T34A particle exhibited superior antitumor effect regarding its DNA plasmid counterpart with high safety.Conclusion: Our results indicated the high delivery capacity of liposome-protamine lipoplex and further suggested CLPP/mSur-T34A mRNA formulation to be a potential candidate for colon cancer therapy.Keywords: mRNA gene therapy, colon cancer, nonviral vector, systemic delivery
format	article
author	Zhang X Men K Zhang Y Zhang R Yang L Duan X
author_facet	Zhang X Men K Zhang Y Zhang R Yang L Duan X
author_sort	Zhang X
title	Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy
title_short	Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy
title_full	Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy
title_fullStr	Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy
title_full_unstemmed	Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy
title_sort	local and systemic delivery of mrna encoding survivin-t34a by lipoplex for efficient colon cancer gene therapy
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/f96a93c8e95e43cbae6d657cd631d78a
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Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy

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