N(1)-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice.
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TLDR
It is found that mRNAs containing the N(1)-methylpseudouridine (m1Ψ) modification alone and/or in combination with 5-methylcytidine ( m5C) outperformed the current state-of-the-art pseudouridine-based mRNA platform and may serve as a new standard in the field of modified mRNA-based therapeutics.About:
This article is published in Journal of Controlled Release.The article was published on 2015-11-10 and is currently open access. It has received 309 citations till now. The article focuses on the topics: Reporter gene & Pseudouridine.read more
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mRNA vaccines — a new era in vaccinology
TL;DR: A detailed overview of mRNA vaccines is provided and future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use are considered.
Journal ArticleDOI
Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination
Norbert Pardi,Michael J. Hogan,Rebecca S. Pelc,Hiromi Muramatsu,Hanne Andersen,Christina R. DeMaso,Kimberly A. Dowd,Laura L. Sutherland,Richard M. Scearce,Robert Parks,Wendeline Wagner,Alex Granados,Jack Greenhouse,Michelle Walker,Elinor Willis,Jae-Sung Yu,Charles E. McGee,Gregory D. Sempowski,Barbara L. Mui,Ying K. Tam,Yan Jang Huang,Dana L. Vanlandingham,Veronica M. Holmes,Harikrishnan Balachandran,Sujata Sahu,Michelle A. Lifton,Stephen Higgs,Scott E. Hensley,Thomas D. Madden,Michael J. Hope,Katalin Karikó,Sampa Santra,Barney S. Graham,Mark G. Lewis,Theodore C. Pierson,Barton F. Haynes,Drew Weissman +36 more
TL;DR: It is demonstrated that a single low-dose intradermal immunization with nucleoside-modified mRNA–LNP elicits rapid and durable protective immunity and therefore represents a new and promising vaccine candidate for the global fight against ZIKV.
Transcriptome-wide Mapping Reveals Widespread Dynamic-Regulated Pseudouridylation of ncRNA and mRNA
Schraga Schwartz,Douglas A. Bernstein,Maxwell R. Mumbach,Marko Jovanovic,Rebecca H. Herbst,Brian X. León-Ricardo,Jesse M. Engreitz,Mitchell Guttman,Rahul Satija,Eric S. Lander,Gerald R. Fink,Aviv Regev,Aviv Regev,Aviv Regev +13 more
TL;DR: This work identifies an enhanced, transcriptome-wide scope for pseudouridine and methods to dissect its underlying mechanisms and function and discovers hundreds of unique sites in human and yeast mRNAs and snoRNAs.
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Advances in the delivery of RNA therapeutics: from concept to clinical reality.
TL;DR: The challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, are discussed, and an overview of the applications of RNAs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic are presented.
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Tools for translation: non-viral materials for therapeutic mRNA delivery
TL;DR: An overview of the field of mRNA therapeutics is provided and recent advances in the development of synthetic materials that encapsulate and deliver mRNA payloads are described.
References
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Journal ArticleDOI
Direct gene transfer into mouse muscle in vivo.
Jon A. Wolff,Robert W. Malone,Phillip Williams,Wang Chong,Gyula Acsadi,Agnes Jani,Philip L. Felgner +6 more
TL;DR: RNA and DNA expression vectors containing genes for chloramphenicol acetyltransferase, luciferase, and beta-galactosidase were separately injected into mouse skeletal muscle in vivo and expression was comparable to that obtained from fibroblasts transfected in vitro under optimal conditions.
Journal ArticleDOI
N6-methyladenosine-dependent regulation of messenger RNA stability
Xiao Wang,Zhike Lu,Adrian Gomez,Gary C. Hon,Yanan Yue,Dali Han,Ye Fu,Marc Parisien,Qing Dai,Guifang Jia,Bing Ren,Tao Pan,Chuan He +12 more
TL;DR: It is shown that m6A is selectively recognized by the human YTH domain family 2 (YTHDF2) ‘reader’ protein to regulate mRNA degradation and established the role of YTH DF2 in RNA metabolism, showing that binding of Y THDF2 results in the localization of bound mRNA from the translatable pool to mRNA decay sites, such as processing bodies.
Journal ArticleDOI
Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA
Luigi Warren,Philip D. Manos,Philip D. Manos,Tim Ahfeldt,Tim Ahfeldt,Yuin-Han Loh,Hu Li,Hu Li,Frank H. Lau,Wataru Ebina,Pankaj Mandal,Zachary D. Smith,Alexander Meissner,Alexander Meissner,George Q. Daley,Andrew S. Brack,James J. Collins,James J. Collins,James J. Collins,Chad A. Cowan,Thorsten M. Schlaeger,Thorsten M. Schlaeger,Derrick J. Rossi +22 more
TL;DR: It is shown that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols and represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine.
Journal ArticleDOI
N6-methyladenosine Modulates Messenger RNA Translation Efficiency
Xiao Wang,Xiao Wang,Boxuan Simen Zhao,Boxuan Simen Zhao,Ian A Roundtree,Ian A Roundtree,Zhike Lu,Zhike Lu,Dali Han,Dali Han,Honghui Ma,Honghui Ma,Xiaocheng Weng,Xiaocheng Weng,Kai Chen,Kai Chen,Hailing Shi,Hailing Shi,Chuan He,Chuan He +19 more
TL;DR: In a unified mechanism of m(6)A-based regulation in the cytoplasm, YTHDF2-mediated degradation controls the lifetime of target transcripts, whereasYTHDF1-mediated translation promotion increases translation efficiency, ensuring effective protein production from dynamic transcripts that are marked by m( 6)A.
Journal ArticleDOI
Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA
TL;DR: It is concluded that nucleoside modifications suppress the potential of RNA to activate DCs, and the innate immune system may detect RNA lacking nucleosides modification as a means of selectively responding to bacteria or necrotic tissue.