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.
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.
Anderson, Bart R.; Muramatsu, Hiromi; Jha, Babal K.; Silverman, Robert H.; Weissman, Drew; Karikó, Katalin . Nucleoside modifications in RNA limit activation of 2'-5'-oligoadenylate synthetase and increase resistance to cleavage by RNase L.
Karikó, Katalin; Muramatsu, Hiromi; Ludwig, János; Weissman, Drew . Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA.
Uchida, Satoshi; Itaka, Keiji; Uchida, Hirokuni; Hayakawa, Kentaro; Ogata, Toru; Ishii, Takehiko; Fukushima, Shigeto; Osada, Kensuke; Kataoka, Kazunori . In vivo messenger RNA introduction into the central nervous system using polyplex nanomicelle.
Guo, Xing Rong; Wang, Xiao Li; Li, Man Chol; Yuan, Ya Hong; Chen, Yun; Zou, Dan Dan; Bian, Liu Jiao; Li, Dong Sheng . PDX-1 mRNA-induced reprogramming of mouse pancreas-derived mesenchymal stem cells into insulin-producing cells in vitro.
Wang, Xiao Li; Hu, Pei; Guo, Xing Rong; Yan, Ding; Yuan, Yahong; Yan, Shi Rong; Li, Dong Sheng . Reprogramming human umbilical cord mesenchymal stromal cells to islet-like cells with the use of in vitro–synthesized pancreatic-duodenal homebox 1 messenger RNA
Hausburg, Frauke; Na, Silke; Voronina, Natalia; Skorska, Anna; Müller, Paula; Steinhoff, Gustav; David, Robert . Defining optimized properties of modified mRNA to enhance virus- and DNA- independent protein expression in adult stem cells and fibroblasts.
Lee, Kunwoo; Yu, Pengzhi; Lingampalli, Nithya; Kim, Hyun Jin; Tang, Richard; Murthy, Niren . Peptide-enhanced mRNA transfection in cultured mouse cardiac fibroblasts and direct reprogramming towards cardiomyocyte-like cells.
Michel, Tatjana; Kankura, Anna; Salinas Medina, Martha L.; Kurz, Julia; Behring, Andreas; Avci-Adali, Meltem; Nolte, Andrea; Schlensak, Christian; Wendel, Hans Peter; Krajewski, Stefanie . In Vitro Evaluation of a Novel mRNA-Based Therapeutic Strategy for the Treatment of Patients Suffering from Alpha-1-Antitrypsin Deficiency.
Pratico, Elizabeth D.; Feger, Bryan J.; Watson, Michael J.; Sullenger, Bruce A.; Bowles, Dawn E.; Milano, Carmelo A.; Nair, Smita K. . RNA-Mediated Reprogramming of Primary Adult Human Dermal Fibroblasts into c-kit(+) Cardiac Progenitor Cells.
Andries, Oliwia; Mc Cafferty, Séan; De Smedt, Stefaan C.; Weiss, Ron; Sanders, Niek N.; Kitada, Tasuku . N(1)-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice.
Poleganov, Marco Alexander; Eminli, Sarah; Beissert, Tim; Herz, Stephanie; Moon, Jung-Il; Goldmann, Johanna; Beyer, Arianne; Heck, Rosario; Burkhart, Isabell; Barea Roldan, Diana; Türeci, Özlem; Yi, Kevin; Hamilton, Brad; Sahin, Ugur . Efficient Reprogramming of Human Fibroblasts and Blood-Derived Endothelial Progenitor Cells Using Nonmodified RNA for Reprogramming and Immune Evasion.
Abraham, Meike-Kristin; Nolte, Andrea; Reus, Rebekka; Behring, Andreas; Zengerle, Diane; Avci-Adali, Meltem; Hohmann, Jan David; Peter, Karlheinz; Schlensak, Christian; Wendel, Hans Peter; Krajewski, Stefanie . In vitro Study of a Novel Stent Coating Using Modified CD39 Messenger RNA to Potentially Reduce Stent Angioplasty-Associated Complications.
Koblas, Tomas; Leontovyc, Ivan; Loukotova, Sarka; Kosinova, Lucie; Saudek, Frantisek . Reprogramming of Pancreatic Exocrine Cells AR42J Into Insulin-producing Cells Using mRNAs for Pdx1, Ngn3, and MafA Transcription Factors.
Dykstra, Brad; Lee, Jungmin; Mortensen, Luke J.; Yu, Haixiao; Wu, Zhengliang L.; Lin, Charles P.; Rossi, Derrick J.; Sackstein, Robert . Glycoengineering of E-Selectin Ligands by Intracellular versus Extracellular Fucosylation Differentially Affects Osteotropism of Human Mesenchymal Stem Cells.
Kauffman, Kevin J.; Mir, Faryal F.; Jhunjhunwala, Siddharth; Kaczmarek, James C.; Hurtado, Juan E.; Yang, Jung H.; Webber, Matthew J.; Kowalski, Piotr S.; Heartlein, Michael W.; DeRosa, Frank; Anderson, Daniel G. . Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles inÃ‚Â vivo.
Goparaju, Sravan Kumar; Kohda, Kazuhisa; Ibata, Keiji; Soma, Atsumi; Nakatake, Yukhi; Akiyama, Tomohiko; Wakabayashi, Shunichi; Matsushita, Misako; Sakota, Miki; Kimura, Hiromi; Yuzaki, Michisuke; Ko, Shigeru B. H.; Ko, Minoru S. H. . Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors.
Guo, Xing-Rong; Yang, Zhuo-Shun; Tang, Xiang-Jun; Zou, Dan-Dan; Gui, Hui; Wang, Xiao-Li; Ma, Shi-Nan; Yuan, Ya-Hong; Fang, Juan; Wang, Bin; Zhang, Li; Sun, Xu-Yong; Warnock, Garth L.; Dai, Long-Jun; Tu, Han-Jun . The application of mRNA-based gene transfer in mesenchymal stem cell-mediated cytotoxicity of glioma cells.
Michel, Tatjana; Luft, Daniel; Abraham, Meike-Kristin; Reinhardt, Sabrina; Salinas Medina, Martha L.; Kurz, Julia; Schaller, Martin; Avci-Adali, Meltem; Schlensak, Christian; Peter, Karlheinz; Wendel, Hans Peter; Wang, Xiaowei; Krajewski, Stefanie . Cationic Nanoliposomes Meet mRNA: Efficient Delivery of Modified mRNA Using Hemocompatible and Stable Vectors for Therapeutic Applications.
Leontovyc, Ivan; Habart, David; Loukotova, Sarka; Kosinova, Lucie; Kriz, Jan; Saudek, Frantisek; Koblas, Tomas . Synthetic mRNA is a more reliable tool for the delivery of DNA-targeting proteins into the cell nucleus than fusion with a protein transduction domain.
Chen, Jiahuan; Fu, Yi; Day, Daniel S.; Sun, Ye; Wang, Shiyan; Liang, Xiaodong; Gu, Fei; Zhang, Fang; Stevens, Sean M.; Zhou, Pingzhu; Li, Kai; Zhang, Yan; Lin, Ruei-Zeng; Smith, Lois E. H.; Zhang, Jin; Sun, Kun; Melero-Martin, Juan M.; Han, Zeguang; Park, Peter J.; Zhang, Bing; Pu, William T. . VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis.
Shibata, Tomonori; Fujita, Yoshihiko; Ohno, Hirohisa; Suzuki, Yuki; Hayashi, Karin; Komatsu, Kaoru R.; Kawasaki, Shunsuke; Hidaka, Kumi; Yonehara, Shin; Sugiyama, Hiroshi; Endo, Masayuki; Saito, Hirohide . Protein-driven RNA nanostructured devices that function in vitro and control mammalian cell fate.
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.
Kogut, Igor; McCarthy, Sandra M.; Pavlova, Maryna; Astling, David P.; Chen, Xiaomi; Jakimenko, Ana; Jones, Kenneth L.; Getahun, Andrew; Cambier, John C.; Pasmooij, Anna M. G.; Jonkman, Marcel F.; Roop, Dennis R.; Bilousova, Ganna . High-efficiency RNA-based reprogramming of human primary fibroblasts.
Suknuntha, Kran; Tao, Lihong; Brok-Volchanskaya, Vera; D'Souza, Saritha S.; Kumar, Akhilesh; Slukvin, Igor . Optimization of Synthetic mRNA for Highly Efficient Translation and its Application in the Generation of Endothelial and Hematopoietic Cells from Human and Primate Pluripotent Stem Cells.
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.
Heinz, Sven; Texari, Lorane; Hayes, Michael G. B.; Urbanowski, Matthew; Chang, Max W.; Givarkes, Ninvita; Rialdi, Alexander; White, Kris M.; Albrecht, Randy A.; Pache, Lars; Marazzi, Ivan; García-Sastre, Adolfo; Shaw, Megan L.; Benner, Christopher . Transcription Elongation Can Affect Genome 3D Structure.
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.