Pseudouridine (5-ribosyluracil) was the first modified ribonucleoside discovered. It is the most abundant natural modified RNA base, and has been deemed the "fifth nucleoside" in RNA. It can be found in structural RNAs, such as transfer, ribosomal and small nuclear RNA. Pseudouridine has been found to enhance base stacking and translation. Pseudouridine-5'-triphosphate (Pseudo-UTP) is used to impart desirable mRNA characteristics such as increased nuclease stability, increased translation or altered interaction of innate immune receptors with in vitro transcribed RNA. Pseudo-UTP, along with 5-methylcytidine-5'-triphosphate (5-methyl-CTP) has shown innate immune suppression in culture and in vivo while enhancing translation in recent publications. For example, Warren et al. determined an efficient means of reprogramming multiple human cell types using modified mRNA that can express the four primary reprogramming proteins. These cells are referred to as induced pluripotency stem cells (iPSCs). Warren et al. found that enzymatically synthesized RNA substituted with Pseudo-UTP, 5-Methyl-CTP and ARCA effectively evaded the cell’s innate immune response, a crucial component in their success. Reduced toxicity due to substitution with Pseudo-UTP, 5-Methyl-CTP was critical since it allowed repeated transfection with in vitro transcribed mRNA over several weeks.
Katalin Karikó, prominent mRNA researcher, references TriLink as a leading manufacturer of Pseudo-UTP; "We value TriLink, it is an excellent company indeed. The product is very good and the customer service is very good too... everybody I know who is making pseudoU RNA is getting it from you."
|Purity||≥97% by AX-HPLC|
|Extinction Coefficient||7,546 Lmol-1cm-1 at 262 nm|
|Molecular Formula||C9H15N2O15P3 (free acid)|
|Molecular Weight||484.10 g/mole (free acid)|
|Recommended Storage||-20°C or below|
|Other Name(s)||Pseudo-UTP, 5-Ribosyl Uracil|
|Application||Aptamers, Epigenetics/DNA Damage, In vitro Transcription, Mutagenesis, Photocrosslinking Studies|
|Nucleotide Category||Base Modified RNA|
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Madore, E.; Florentz, C.; Giegé, R.; Sekine, S.; Yokoyama, S.; Lapointe, J. . Effect of modified nucleotides on Escherichia coli tRNAGlu structure and on its aminoacylation by glutamyl-tRNA synthetase. Predominant and distinct roles of the mnm5 and s2 modifications of U34.
Karikó, Katalin; Muramatsu, Hiromi; Welsh, Frank A.; Ludwig, János; Kato, Hiroki; Akira, Shizuo; Weissman, Drew . Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability.
Karikó, Katalin; Buckstein, Michael; Ni, Houping; Weissman, Drew . Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA.
Anderson, Bart R.; Muramatsu, Hiromi; Nallagatla, Subba R.; Bevilacqua, Philip C.; Sansing, Lauren H.; Weissman, Drew; Karikó, Katalin . Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation.
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Karikó, Katalin; Muramatsu, Hiromi; Keller, Jason M.; Weissman, Drew . Increased erythropoiesis in mice injected with submicrogram quantities of pseudouridine-containing mRNA encoding erythropoietin.
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Wang, Yuhua; Zhang, Lu; Xu, Zhenghong; Miao, Lei; Huang, Leaf . mRNA Vaccine with Antigen-Specific Checkpoint Blockade Induces an Enhanced Immune Response against Established Melanoma.
Liu, Lina; Wang, Yuhua; Miao, Lei; Liu, Qi; Musetti, Sara; Li, Jun; Huang, Leaf . Combination Immunotherapy of MUC1 mRNA Nano-vaccine and CTLA-4 Blockade Effectively Inhibits Growth of Triple Negative Breast Cancer.
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Potapov, Vladimir; Fu, Xiaoqing; Dai, Nan; Corrêa, Ivan R. Jr; Tanner, Nathan A.; Ong, Jennifer L. . Base modifications affecting RNA polymerase and reverse transcriptase fidelity.
Golombek, Sonia; Pilz, Martin; Steinle, Heidrun; Kochba, Efrat; Levin, Yotam; Lunter, Dominique; Schlensak, Christian; Wendel, Hans Peter; Avci-Adali, Meltem . Intradermal Delivery of Synthetic mRNA Using Hollow Microneedles for Efficient and Rapid Production of Exogenous Proteins in Skin.
Mondal, Nandini; Dykstra, Brad; Lee, Jungmin; Ashline, David J.; Reinhold, Vernon N.; Rossi, Derrick J.; Sackstein, Robert . Distinct human ÃŽÂ±(1,3)-fucosyltransferases drive Lewis-X/sialyl Lewis-X assembly in human cells.
Steinle, Heidrun; Ionescu, Tudor-Mihai; Schenk, Selina; Golombek, Sonia; Kunnakattu, Silju-John; Özbek, Melek Tutku; Schlensak, Christian; Wendel, Hans Peter; Avci-Adali, Meltem . Incorporation of Synthetic mRNA in Injectable Chitosan-Alginate Hybrid Hydrogels for Local and Sustained Expression of Exogenous Proteins in Cells.
Kim, Bo-Eun; Choi, Soon Won; Shin, Ji-Hee; Kim, Jae-Jun; Kang, Insung; Lee, Byung-Chul; Lee, Jin Young; Kook, Myoung Geun; Kang, Kyung-Sun . Single-Factor SOX2 Mediates Direct Neural Reprogramming of Human Mesenchymal Stem Cells via Transfection of In Vitro Transcribed mRNA.
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Loomis, Kristin H.; Lindsay, Kevin E.; Zurla, Chiara; Bhosle, Sushma M.; Vanover, Daryll A.; Blanchard, Emmeline L.; Kirschman, Jonathan L.; Bellamkonda, Ravi V.; Santangelo, Philip J. . In Vitro Transcribed mRNA Vaccines with Programmable Stimulation of Innate Immunity.
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Zhao, W;Zeng, C;Yan, J;Du, S;Hou, X;Zhang, C;Li, W;Deng, B;McComb, DW;Xue, Y;Kang, DD;Dong, Y; . Construction of Messenger RNA (mRNA) Probes Delivered By Lipid Nanoparticles to Visualize Intracellular Protein Expression and Localization at Organelles
Zhang, X;Zhao, W;Nguyen, G;Zhang, C;Zeng, C;Yan, J;Du, S;Hou, X;Li, W;Jiang, J;Deng, B;McComb, D;Dorkin, R;Shah, A;Barrera, L;Gregoire, F;Singh, M;Chen, D;Sabatino, D;Dong, Y; . Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing
Li, B;Zeng, C;Dong, Y; . Design and assessment of engineered CRISPR-Cpf1 and its use for genome editing
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Wang, P;Logeart-Avramoglou, D;Petite, H;Goncalves, C;Midoux, P;Perche, F;Pichon, C; . Co-delivery of NS1 and BMP2 mRNAs to murine pluripotent stem cells leads to enhanced BMP-2 expression and osteogenic differentiation
Lockhart, J;Canfield, J;Mong, EF;VanWye, J;Totary-Jain, H; . Nucleotide Modification Alters MicroRNA-Dependent Silencing of MicroRNA Switches
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Michel, T;Luft, D;Abraham, MK;Reinhardt, S;Salinas Medina, ML;Kurz, J;Schaller, M;Avci-Adali, M;Schlensak, C;Peter, K;Wendel, HP;Wang, X;Krajewski, S; . Cationic nanoliposomes meet mRNA: Efficient delivery of modified mRNA using hemocompatible and stable vectors for therapeutic applications
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Zhang, M;Sun, J;Li, M;Jin, X; . Modified mRNA-LNP vaccines confer protection against experimental DENV-2 infection in mice
Sadegh, C;Ebina, W;Arvanites, AC;Davidow, LS;Rubin, LL;Macklis, JD; . Synthetic modified Fezf2 mRNA (modRNA) with concurrent small molecule SIRT1 inhibition enhances refinement of cortical subcerebral/corticospinal neuron identity from mouse embryonic stem cells
Leppek, K;Byeon, GW;Kladwang, W;Wayment-Steele, HK;Kerr, CH;Xu, AF;Kim, DS;Topkar, VV;Choe, C;Rothschild, D;Tiu, GC;Wellington-Oguri, R;Fujii, K;Sharma, E;Watkins, AM;Nicol, JJ;Romano, J;Tunguz, B;Participants, E;Barna, M;Das, R; . Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
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Zhang, W; . Investigation and Characterization of RNA Modifications
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Svitkin, YV;Gingras, AC;Sonenberg, N; . Membrane-dependent relief of translation elongation
Lin, X;Chen, H;Xie, Y;Zhou, X;Wang, Y;Zhou, J;Long, S;Hu, Z;Zhang, S;Qiu, W;Zeng, Z;Liu, L; . Combination of CTLA-4 blockade with MUC1 mRNA nanovaccine induces enhanced anti-tumor CTL activity by modulating tumor microenvironment of triple negative breast cancer
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Peng, H;Guo, X;He, J;Duan, C;Yang, M;Zhang, X;Zhang, L;Fu, R;Wang, B;Wang, D;Chen, H;Xie, M;Feng, P;Dai, L;Tang, X;Luo, J; . Intracranial delivery of synthetic mRNA to suppress glioblastoma
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Yang, J;Ding, S; . Chimeric RNA binding protein based killing switch targeting hepatocellular carcinoma cells