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

Tongren Yang; Chunhui Li; Xiaoxia Wang; Deyao Zhao; Mengjie Zhang; Huiqing Cao; Zicai Liang; Haihua Xiao; Xing Jie Liang; Yuhua Weng; Yuanyu Huang

doi:10.1016/j.bioactmat.2020.07.003

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

Tongren Yang, Chunhui Li, Xiaoxia Wang, Deyao Zhao, Mengjie Zhang, Huiqing Cao, Zicai Liang, Haihua Xiao, Xing Jie Liang, Yuhua Weng^*, Yuanyu Huang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

66 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1053-1061
Number of pages	9
Journal	Bioactive Materials
Volume	5
Issue number	4
DOIs	https://doi.org/10.1016/j.bioactmat.2020.07.003
Publication status	Published - Dec 2020

Keywords

Codon optimization
Erythropoietin
Lipid nanoparticle
mRNA delivery
mRNA therapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bioactmat.2020.07.003

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title = "Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle",

abstract = "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.",

keywords = "Codon optimization, Erythropoietin, Lipid nanoparticle, mRNA delivery, mRNA therapy",

author = "Tongren Yang and Chunhui Li and Xiaoxia Wang and Deyao Zhao and Mengjie Zhang and Huiqing Cao and Zicai Liang and Haihua Xiao and Liang, {Xing Jie} and Yuhua Weng and Yuanyu Huang",

note = "Publisher Copyright: {\textcopyright} 2020 [The Author/The Authors]",

year = "2020",

month = dec,

doi = "10.1016/j.bioactmat.2020.07.003",

language = "English",

volume = "5",

pages = "1053--1061",

journal = "Bioactive Materials",

issn = "2452-199X",

publisher = "KeAi Communications Co.",

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TY - JOUR

T1 - Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle

AU - Yang, Tongren

AU - Li, Chunhui

AU - Wang, Xiaoxia

AU - Zhao, Deyao

AU - Zhang, Mengjie

AU - Cao, Huiqing

AU - Liang, Zicai

AU - Xiao, Haihua

AU - Liang, Xing Jie

AU - Weng, Yuhua

AU - Huang, Yuanyu

PY - 2020/12

Y1 - 2020/12

N2 - 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.

AB - 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.

KW - Codon optimization

KW - Erythropoietin

KW - Lipid nanoparticle

KW - mRNA delivery

KW - mRNA therapy

UR - http://www.scopus.com/inward/record.url?scp=85087755438&partnerID=8YFLogxK

U2 - 10.1016/j.bioactmat.2020.07.003

DO - 10.1016/j.bioactmat.2020.07.003

M3 - Article

AN - SCOPUS:85087755438

SN - 2452-199X

VL - 5

SP - 1053

EP - 1061

JO - Bioactive Materials

JF - Bioactive Materials

IS - 4

ER -

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

Abstract

Keywords

UN SDGs

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