title: Effects of Chemically Modified Messenger RNA on Protein Expression.
abstract: Chemically modified nucleotides play significant roles in the effectiveness of mRNA translation. Here, we describe the synthesis of two sets of chemically modified mRNAs [encoding firefly Luciferase (FLuc) and enhanced green fluorescent protein (eGFP), respectively], evaluation of protein expression, and correlation analysis of expression level under various conditions. The results indicate that chemical modifications of mRNAs are able to significantly improve protein expression, which is dependent on cell types and coding sequences. Moreover, eGFP mRNAs with N1-methylpseudouridine (me(1)ψ), 5-methoxyuridine (5moU), and pseudouridine (ψ) modifications ranked top three in cell lines tested. Interestingly, 5moU-modified eGFP mRNA was more stable than other eGFP mRNAs. Consequently, me(1)ψ, 5moU, and ψ are promising nucleotides for chemical modification of mRNAs.
authors.affiliation: Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, ‡Department of Biomedical Engineering, §The Center for Clinical and Translational Science, and ∥The Comprehensive Cancer Center, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, ‡Department of Biomedical Engineering, §The Center for Clinical and Translational Science, and ∥The Comprehensive Cancer Center, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Xiao
authors.initials: X
authors.lastname: Luo
authors.affiliation: Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, ‡Department of Biomedical Engineering, §The Center for Clinical and Translational Science, and ∥The Comprehensive Cancer Center, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Dong
mesh_terms: D002460:Cell Line; D006801:Humans; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D011506:Proteins; D012333:RNA, Messenger