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Open AccessArticle

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

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Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
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Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
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Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
*
Authors to whom correspondence should be addressed.
Academic Editor: Afzal R. Mohammed
Pharmaceutics 2015, 7(3), 137-151; https://doi.org/10.3390/pharmaceutics7030137
Received: 3 June 2015 / Revised: 15 July 2015 / Accepted: 17 July 2015 / Published: 23 July 2015
(This article belongs to the Special Issue New Paradigm of Gene Therapy)
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. View Full-Text
Keywords: mRNA; modification; immunogenicity; translation efficiency; nuclease-mediated degradation mRNA; modification; immunogenicity; translation efficiency; nuclease-mediated degradation
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Uchida, S.; Kataoka, K.; Itaka, K. Screening of mRNA Chemical Modification to Maximize Protein Expression with Reduced Immunogenicity. Pharmaceutics 2015, 7, 137-151.

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