N1-Methylpseudouridine-5'-triphosphate

Methylpseudouridine-5'-triphosphate, N1mΨ-TP, N1meΨTP, m1ΨTP, 1-Methylpseudo-UTP, N1-Methyl-Pseudouridine-5'-Triphosphate

N1-Methylpseudouridine-5'-triphosphate is supplied as the triethylammonium salt in aqueous solution with the amount and concentration written on the label. Aqueous solution is the most stable form for di and triphosphates.

For a quotation for larger amounts please inquire.

You may place your order online or by telephone.

$69/1 micromole)
$315/5 micromoles)
$437/10 micromoles)
$720/20 micromoles)
$2598/100 micromoles)

Overview of N1-Methylpseudouridine-5'-triphosphate

N1-Methylpseudouridine-5'-triphosphate (N1mΨ-TP) is an analog nucleotide used in the field of mRNA therapeutics and vaccine development to incorporate N1-Methylpseudouridine into synthetic messenger RNA in place of pseudouridine. When incorporated into mRNA, N1-Methylpseudouridine (N1mΨ) enhances the stability and reduces the degradation of RNA molecules.

Enhanced RNA Stability

Structural Stability: N1mΨ increases the structural rigidity of RNA molecules, making them more resistant to degradation by ribonucleases (RNases). This structural enhancement helps maintain the integrity of RNA for a longer period.

Improved Hydrogen Bonding: The N1-methyl modification can enhance hydrogen bonding within the RNA molecule, contributing to a more stable RNA structure that is less prone to spontaneous degradation.

Reduced Immunogenicity

Immune System Evasion: Incorporating N1mΨ into RNA sequences helps the RNA evade detection by the innate immune system. This reduction in immune recognition decreases the likelihood of RNA being targeted for degradation by immune-related enzymes.

Decreased Activation of RNA Sensors: N1mΨ-modified RNA is less likely to activate RNA sensors such as Toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) that can lead to RNA degradation.

Applications in mRNA Therapeutics and Vaccines

mRNA Stability in Vaccines: N1mΨ is used in mRNA vaccines, such as those developed for COVID-19 by Pfizer-BioNTech and Moderna. The incorporation of N1mΨ significantly enhances the stability of the mRNA, ensuring it remains intact long enough to be translated into the target protein within the body.

Increased Protein Expression: The stability provided by N1mΨ allows for higher and more sustained levels of protein expression from the mRNA. This is critical for the effectiveness of mRNA-based therapeutics, ensuring the desired therapeutic proteins are produced efficiently.

Mechanisms of Action

Ribonuclease Resistance: The presence of N1mΨ in RNA sequences makes them less susceptible to cleavage by RNases. This resistance to enzymatic degradation is one of the primary reasons for the increased stability of N1mΨ-modified RNA.

Enhanced Translation Efficiency: N1mΨ not only stabilizes RNA but also improves its translation efficiency. The modifications help in forming more stable and efficient translation initiation complexes, leading to more effective protein synthesis.

Research and Development

Synthetic RNA: Researchers are leveraging N1mΨ to design more stable synthetic RNA molecules for various applications, including gene therapy, RNA-based therapeutics, and synthetic biology.

Long-Term Expression: N1mΨ-modified RNA can sustain long-term expression of therapeutic proteins, which is advantageous for chronic conditions and long-lasting vaccine responses.

Summary

N1-Methylpseudouridine is a crucial modification that significantly enhances the stability and reduces the degradation of RNA molecules. Its use in mRNA vaccines and therapeutics improves the efficiency and longevity of these treatments, making them more effective and reliable. By providing resistance to degradation and reducing immunogenicity, N1mΨ plays a pivotal role in advancing RNA-based medical applications.