Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32691013.
- Also identified by DOI 10.1016/j.bioactmat.2020.07.003 and PMC identifier 7355334.
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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 <i>etc.</i> However, optimization of mRNA molecules and efficient <i>in vivo</i> delivery are quite important but challenging for its broad application. Here we present an ionizable lipid nanoparticle (iLNP) based on iBL0713 lipid for <i>in vitro</i> and <i>in vivo</i> expression of desired proteins using codon-optimized mRNAs. mRNAs encoding luciferase or erythropoietin (EPO) were prepared by <i>in vitro</i> 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.