Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle
Date
2020Author
Yang, Tongren
Li, Chunhui
Wang, Xiaoxia
Zhao, Deyao
Zhang, Mengjie
Cao, Huiqing
Liang, Zicai
Xiao, Haihua
Liang, Xing-Jie
Weng, Yuhua
Huang, Yuanyu
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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.
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https://doi.org/10.1016/j.bioactmat.2020.07.003Collections
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