Effects of Chemically Modified Messenger RNA on Protein Expression

被引：113
作者：
Li, Bin [1 ]
Luo, Xiao [1 ]
Dong, Yizhou [1 ,2 ,3 ,4 ]
机构：
[1] Ohio State Univ, Div Pharmaceut & Pharmaceut Chem, Coll Pharm, Columbus, OH 43210 USA
[2] Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA
[3] Ohio State Univ, Ctr Clin & Translat Sci, Columbus, OH 43210 USA
[4] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
来源：
BIOCONJUGATE CHEMISTRY | 2016年 / 27卷 / 03期
关键词：
DELIVERY IN-VIVO; PROGENITOR CELLS; PSEUDOURIDINE; THERAPY; MICE; OPTIMIZATION;
D O I：
10.1021/acs.bioconjchem.6b00090
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
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 N-1-methylpseudouridine (melig), 5-methoxyuridine (me(1)psi), and pseudouridine (psi) modifications ranked top three in cell lines tested. Interestingly, SmoU-modified eGFP mRNA was more stable than other eGFP mRNAs. Consequently, me(1)psi, SmoU, and psi are promising nucleotides for chemical modification of mRNAs.
引用
收藏
页码：849 / 853
页数：5
相关论文
共 21 条
  • [1] Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation
    Anderson, Bart R.
    Muramatsu, Hiromi
    Nallagatla, Subba R.
    Bevilacqua, Philip C.
    Sansing, Lauren H.
    Weissman, Drew
    Kariko, Katalin
    [J]. NUCLEIC ACIDS RESEARCH, 2010, 38 (17) : 5884 - 5892
  • [2] N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice
    Andries, Oliwia
    Mc Cafferty, Sean
    De Smedt, Stefaan C.
    Weiss, Ron
    Sanders, Niek N.
    Kitada, Tasuku
    [J]. JOURNAL OF CONTROLLED RELEASE, 2015, 217 : 337 - 344
  • [3] Clinical use of dendritic cells for cancer therapy
    Anguille, Sebastien
    Smits, Evelien L.
    Lion, Eva
    van Tendeloo, Viggo F.
    Berneman, Zwi N.
    [J]. LANCET ONCOLOGY, 2014, 15 (07) : E257 - E267
  • [4] Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells
    Hendel, Ayal
    Bak, Rasmus O.
    Clark, Joseph T.
    Kennedy, Andrew B.
    Ryan, Daniel E.
    Roy, Subhadeep
    Steinfeld, Israel
    Lunstad, Benjamin D.
    Kaiser, Robert J.
    Wilkens, Alec B.
    Bacchetta, Rosa
    Tsalenko, Anya
    Dellinger, Douglas
    Bruhn, Laurakay
    Porteus, Matthew H.
    [J]. NATURE BIOTECHNOLOGY, 2015, 33 (09) : 985 - U232
  • [5] Biomaterials for mRNA delivery
    Islam, Mohammad Ariful
    Reesor, Emma K. G.
    Xu, Yingjie
    Zope, Harshal R.
    Zetter, Bruce R.
    Shi, Jinjun
    [J]. BIOMATERIALS SCIENCE, 2015, 3 (12) : 1519 - 1533
  • [6] mRNA is an endogenous ligand for Toll-like receptor 3
    Karikó, K
    Ni, HP
    Capodici, J
    Lamphier, M
    Weissman, D
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (13) : 12542 - 12550
  • [7] Incorporation of Pseudouridine Into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability
    Kariko, Katalin
    Muramatsu, Hiromi
    Welsh, Frank A.
    Ludwig, Janos
    Kato, Hiroki
    Akira, Shizuo
    Weissman, Drew
    [J]. MOLECULAR THERAPY, 2008, 16 (11) : 1833 - 1840
  • [8] Increased Erythropoiesis in Mice Injected With Submicrogram Quantities of Pseudouridine-containing mRNA Encoding Erythropoietin
    Kariko, Katalin
    Muramatsu, Hiromi
    Keller, Jason M.
    Weissman, Drew
    [J]. MOLECULAR THERAPY, 2012, 20 (05) : 948 - 953
  • [9] Optimization of Lipid Nanoparticle Formulations for mRNA Delivery in Vivo with Fractional Factorial and Definitive Screening Designs
    Kauffman, Kevin J.
    Dorkin, J. Robert
    Yang, Jung H.
    Heartlein, Michael W.
    DeRosa, Frank
    Mir, Faryal F.
    Fenton, Owen S.
    Anderson, Daniel G.
    [J]. NANO LETTERS, 2015, 15 (11) : 7300 - 7306
  • [10] Expression of therapeutic proteins after delivery of chemically modified mRNA in mice
    Kormann, Michael S. D.
    Hasenpusch, Guenther
    Aneja, Manish K.
    Nica, Gabriela
    Flemmer, Andreas W.
    Herber-Jonat, Susanne
    Huppmann, Marceline
    Mays, Lauren E.
    Illenyi, Marta
    Schams, Andrea
    Griese, Matthias
    Bittmann, Iris
    Handgretinger, Rupert
    Hartl, Dominik
    Rosenecker, Joseph
    Rudolph, Carsten
    [J]. NATURE BIOTECHNOLOGY, 2011, 29 (02) : 154 - U96
123