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Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle

mRNA is a novel class of therapeutic modality that holds great promise in vaccination, protein replacement therapy, cancer immunotherapy, immune cell engineering etc. However, optimization of mRNA molecules and efficient in vivo delivery are quite important but challenging for its broad application....

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Detalles Bibliográficos
Autores principales: Yang, Tongren, Li, Chunhui, Wang, Xiaoxia, Zhao, Deyao, Zhang, Mengjie, Cao, Huiqing, Liang, Zicai, Xiao, Haihua, Liang, Xing-Jie, Weng, Yuhua, Huang, Yuanyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355334/
https://www.ncbi.nlm.nih.gov/pubmed/32691013
http://dx.doi.org/10.1016/j.bioactmat.2020.07.003
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author Yang, Tongren
Li, Chunhui
Wang, Xiaoxia
Zhao, Deyao
Zhang, Mengjie
Cao, Huiqing
Liang, Zicai
Xiao, Haihua
Liang, Xing-Jie
Weng, Yuhua
Huang, Yuanyu
author_facet Yang, Tongren
Li, Chunhui
Wang, Xiaoxia
Zhao, Deyao
Zhang, Mengjie
Cao, Huiqing
Liang, Zicai
Xiao, Haihua
Liang, Xing-Jie
Weng, Yuhua
Huang, Yuanyu
author_sort Yang, Tongren
collection PubMed
description mRNA is a novel class of therapeutic modality that holds great promise in vaccination, protein replacement therapy, cancer immunotherapy, immune cell engineering etc. However, optimization of mRNA molecules and efficient in vivo delivery are quite important but challenging for its broad application. Here we present an ionizable lipid nanoparticle (iLNP) based on iBL0713 lipid for in vitro and in vivo expression of desired proteins using codon-optimized mRNAs. mRNAs encoding luciferase or erythropoietin (EPO) were prepared by in vitro transcription and formulated with proposed iLNP, to form iLP171/mRNA formulations. It was revealed that both luciferase and EPO proteins were successfully expressed by human hepatocellular carcinoma cells and hepatocytes. The maximum amount of protein expression was found at 6 h post-administration. The expression efficiency of EPO with codon-optimized mRNA was significantly higher than that of unoptimized mRNA. Moreover, no toxicity or immunogenicity was observed for these mRNA formulations. Therefore, our study provides a useful and promising platform for mRNA therapeutic development.
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spelling pubmed-73553342020-07-13 Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle Yang, Tongren Li, Chunhui Wang, Xiaoxia Zhao, Deyao Zhang, Mengjie Cao, Huiqing Liang, Zicai Xiao, Haihua Liang, Xing-Jie Weng, Yuhua Huang, Yuanyu Bioact Mater Article mRNA is a novel class of therapeutic modality that holds great promise in vaccination, protein replacement therapy, cancer immunotherapy, immune cell engineering etc. However, optimization of mRNA molecules and efficient in vivo delivery are quite important but challenging for its broad application. Here we present an ionizable lipid nanoparticle (iLNP) based on iBL0713 lipid for in vitro and in vivo expression of desired proteins using codon-optimized mRNAs. mRNAs encoding luciferase or erythropoietin (EPO) were prepared by in vitro transcription and formulated with proposed iLNP, to form iLP171/mRNA formulations. It was revealed that both luciferase and EPO proteins were successfully expressed by human hepatocellular carcinoma cells and hepatocytes. The maximum amount of protein expression was found at 6 h post-administration. The expression efficiency of EPO with codon-optimized mRNA was significantly higher than that of unoptimized mRNA. Moreover, no toxicity or immunogenicity was observed for these mRNA formulations. Therefore, our study provides a useful and promising platform for mRNA therapeutic development. KeAi Publishing 2020-07-13 /pmc/articles/PMC7355334/ /pubmed/32691013 http://dx.doi.org/10.1016/j.bioactmat.2020.07.003 Text en © 2020 [The Author/The Authors] http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Yang, Tongren
Li, Chunhui
Wang, Xiaoxia
Zhao, Deyao
Zhang, Mengjie
Cao, Huiqing
Liang, Zicai
Xiao, Haihua
Liang, Xing-Jie
Weng, Yuhua
Huang, Yuanyu
Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle
title Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle
title_full Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle
title_fullStr Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle
title_full_unstemmed Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle
title_short Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle
title_sort efficient hepatic delivery and protein expression enabled by optimized mrna and ionizable lipid nanoparticle
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355334/
https://www.ncbi.nlm.nih.gov/pubmed/32691013
http://dx.doi.org/10.1016/j.bioactmat.2020.07.003
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