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Screening of mRNA Chemical Modification to Maximize Protein Expression with Reduced Immunogenicity

Authors :
Satoshi Uchida
Kazunori Kataoka
Keiji Itaka
Source :
Pharmaceutics, Vol 7, Iss 3, Pp 137-151 (2015)
Publication Year :
2015
Publisher :
MDPI AG, 2015.

Abstract

Chemical modification of nucleosides in mRNA is an important technology to regulate the immunogenicity of mRNA. In this study, various previously reported mRNA formulations were evaluated by analyzing in vitro protein expression and immunogenicity in multiple cell lines. For the macrophage-derived cell line, RAW 264.7, modified mRNA tended to have reduced immunogenicity and increased protein expression compared to the unmodified mRNA. In contrast, in some cell types, such as hepatocellular carcinoma cells (HuH-7) and mouse embryonic fibroblasts (MEFs), protein expression was decreased by mRNA modification. Further analyses revealed that mRNA modifications decreased translation efficiency but increased nuclease stability. Thus, mRNA modification is likely to exert both positive and negative effects on the efficiency of protein expression in transfected cells and optimal mRNA formulation should be determined based on target cell types and transfection purposes.

Details

Language :
English
ISSN :
19994923
Volume :
7
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.75a0429d23884ee4a4c90b97dd861943
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics7030137