RNA base-modified ribonucleoside triphosphate is used in in vitro transcription (IVT) of RNA medicines. RNA vaccines work by inducing the body to express viral proteins, which in turn stimulate the immune system to produce antibodies. In this process, the mRNA's own evasion of the immune system is important, along with the mRNA's translational efficiency. It is known that swapping nucleotides for a related analogue helped to make the mRNA less conspicuous to the immune system.¹⁾
TCI has commercialized N¹-methyl pseudouridine 5'-triphosphate sodium salt (Product No. M3544), pseudouridine 5'-triphosphate sodium salt (Product No. P3045), 5-methyluridine 5'-triphosphate sodium salt (Product No. M3582), 5-methylcytidine 5'-triphosphate sodium salt (Product No. M3583), 5-methoxyuridine 5'-triphosphate sodium salt (Product No. M3584) which are expected to have high translational efficiency and immunogenicity reduction effects, as raw materials for the synthesis of modified RNA medicines.^2-6) These products have been checked for DNase and RNase contamination and functionality in IVT.

In recent years, studies in this field have been very active, new effects of base-modified nucleotides are continuously being reported. TCI is capable of performing the full process from modification of bases to triphosphorylation in-house, and can also provide base-modified triphosphates that are not listed in our catalog. TCI are also available for consultation on scale-up manufacturing.

Products

Page Top

References

• 1) Trial settles debate over best design for mRNA in COVID vaccines
  • E. Dolgin, Nature 2023, 613, 419.
• 2) Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA
  • K. Karikó, M Buckstein, H. Ni, D. Weissman, Immunity 2005, 23, 165.
• 3) Incorporation of Pseudouridine Into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability
  • K. Karikó, H. Muramatsu, F. A Welsh, H. Kato, S. Akira, D. Weissman, Mol. Ther. 2008, 16, 1833.
• 4) Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation
  • B. R. Anderson, H. Muramatsu, S. R. Nallagatla, P. C. Bevilacqua, L. H. Sansing, D. Weissman, K. Karikó, Nucleic Acids Res. 2010, 38, 5884.
• 5) Nucleoside modifications in RNA limit activation of 2'-5'-oligoadenylate synthetase and increase resistance to cleavage by RNase L
  • B. R. Anderson, H. Muramatsu, B. K. Jha, R. H. Silverman, D. Weissman, K. Karikó, Nucleic Acids Res. 2011, 39, 9329.
• 4) Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA
  • K. Karikó, H. Muramatsu, J. Ludwig, D. Weissman, Nucleic Acids Res. 2011, 39, e142.

Page Top

Related Product Category Pages

• Nucleic Acid Chemistry
• Base Modified Nucleosides and Nucleotides

Page Top

Product Brochures

Page Top