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Home » Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer?

Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer?

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New published study by an international team of researchers confirms what some medical experts have been suspecting for 18 months: The COVID mRNA shots containing N1-methyl-pseudouridine suppress the immune system and stimulate cancer growth! [Via: @NikolovScience]

Alberto Rubio-Casillas ab, David Cowley c, Mikolaj Raszek d, Vladimir N. Uversky ef, Elrashdy M. Redwan gh

Received 19 December 2023, Revised 9 February 2024, Accepted 4 April 2024, Available online 5 April 2024, Version of Record 10 April 2024.


Due to the health emergency created by SARS-CoV-2, the virus that causes the COVID-19 disease, the rapid implementation of a new vaccine technology was necessary. mRNA vaccines, being one of the cutting-edge new technologies, attracted significant interest and offered a lot of hope. The potential of these vaccines in preventing admission to hospitals and serious illness in people with comorbidities has recently been called into question due to the vaccines’ rapidly waning immunity. Mounting evidence indicates that these vaccines, like many others, do not generate sterilizing immunity, leaving people vulnerable to recurrent infections. Additionally, it has been discovered that the mRNA vaccines inhibit essential immunological pathways, thus impairing early interferon signaling. Within the framework of COVID-19 vaccination, this inhibition ensures an appropriate spike protein synthesis and a reduced immune activation. Evidence is provided that adding 100 % of N1-methyl-pseudouridine (m1Ψ) to the mRNA vaccine in a melanoma model stimulated cancer growth and metastasis, while non-modified mRNA vaccines induced opposite results, thus suggesting that COVID-19 mRNA vaccines could aid cancer development. Based on this compelling evidence, we suggest that future clinical trials for cancers or infectious diseases should not use mRNA vaccines with a 100 % m1Ψ modification, but rather ones with the lower percentage of m1Ψ modification to avoid immune suppression.


When the COVID-19 pandemic broke out in early 2020, there was an immediate need for COVID-19 vaccines. Creating new vaccine technologies was necessary to increase vaccine effectiveness and decrease production time [1]. mRNA vaccines, one of the cutting-edge new technologies, attracted a lot of interest and offered a lot of hope [2,3]. Fast development and manufacturing speeds were made possible by this technique, which were crucial capabilities that could be successfully employed in biotechnological and therapeutic scenarios [4]. The manufacturing of mRNA vaccines can be completed in a matter of days or weeks as opposed to months or years required for the manufacture of, for example, attenuated or inactivated viruses [5]. It is possible to achieve this using in vitro transcription of mRNA, in which nearly any mRNA sequence may be generated from a DNA template [6,7]. Additionally, an mRNA vaccine would give the cell-specific instructions for using cytoplasmic translation to create a desired immunogenic protein [8]. The development of mRNA therapies, like other nucleic acid-based treatment methods, has been hampered by several delivery challenges. Before arriving at the ribosomes, an RNA molecule, for example, may be destroyed by ribonucleases or captured by endosomes [9]. A further obstacle in the mRNA delivery is related to the RNA crossing biological membranes due to its negatively charged phosphodiester backbone [10].

This problem was resolved by encasing the RNA in a wrap made of lipid nanoparticles (LNPs) and guiding it to the ribosomes. These lipids were explored as delivery systems for RNA to mammalian cells decades ago [[11], [12], [13]]. In addition to the aforementioned delivery difficulties, therapeutic mRNA faced at least two other significant obstacles: When administered to animals, in vitro transcribed (IVT) mRNA would: 1) be susceptible to nuclease breakdown; and 2) induce innate immunogenicity comparable to that experienced when infected by a pathogen [14]. Pseudouridine (Ψ), a widely recognized RNA alteration that can be utilized to substitute uridine in the IVT mRNA, provided a solution to these problems. It has been shown that Ψ inclusion increases RNA stability while concurrently dampening the anti-RNA immune response [15,16]. Since it was shown that the Ψ-modification could help mRNA to avoid innate immune responses [16], a search for Ψ-derivatives with the enhanced characteristics was conducted. As a result, it was discovered that N1-methyl-Ψ (m1Ψ) decreased the functionality of innate immune sensors, and performed properly (and even better than Ψ) when tested in several basic human cells. In mice, m1Ψ enhanced the translational efficiency and lowered the cytotoxicity of modified mRNA delivered intramuscularly and through the skin [17].