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

Bibliographic Details
Title: Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy
Authors: Zhang X, Men K, Zhang Y, Zhang R, Yang L, Duan X
Source: International Journal of Nanomedicine, Vol Volume 14, Pp 2733-2751 (2019)
Publisher Information: Dove Medical Press, 2019.
Publication Year: 2019
Collection: LCC:Medicine (General)
Subject Terms: mRNA gene therapy, colon cancer, non-viral vector, systemic delivery, Medicine (General), R5-920
More Details: 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
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1178-2013
Relation: https://www.dovepress.com/local-and-systemic-delivery-of-mrna-encoding-survivin-t34a-by-lipoplex-peer-reviewed-article-IJN; https://doaj.org/toc/1178-2013
Access URL: https://doaj.org/article/f96a93c8e95e43cbae6d657cd631d78a
Accession Number: edsdoj.f96a93c8e95e43cbae6d657cd631d78a
Database: Directory of Open Access Journals
More Details
ISSN:11782013
Published in:International Journal of Nanomedicine
Language:English