Application review of pseudoUridine and its derivatives

Pseudouridine is the most abundant RNA modification in cellular RNA. Pseudouridine (abbreviated by the Greek letter psi- Ψ) is an isomer of the nucleoside uridine in which the uracil is attached via a carbon-carbon instead of a nitrogen-carbon glycosidic bond. The C-C bond gives it more rotational freedom and conformational flexibility. It has an additional hydrogen bond donor at N1

Pseudouridine has been found in tRNA, rRNA, snRNA, snoRNA and scaRNA, and mRNA. Indeed, chemical and functional characteristics of Ψ itself significantly impacts target RNAs at different levels (from structure to function) by making base pairing easier and, ultimately, increasing duplex stability and influencing secondary structures.

The successful development of a novel COVID-19 vaccine based on messenger RNA (mRNA) paves the way for mRNA technology. In addition to preventive vaccines, mRNA technology could also be used to treat diseases such as cystic fibrosis and cancer. Compared with traditional biotechnology, mRNA vaccine has the advantages of high safety, small variation between batches, fast response
and economical mass production, all of which granting it to be advantageous in dealing with pandemics such as COVID-19. Over the past year, billions of dollars are flowing into the
development of mRNA vaccines and related therapies. A gene therapy revolution is taking place.

mRNA is a transient carrier of genetic information, but mRNA based gene therapy methods have not been popularized at first due to the general instability and immunogenicity of RNA molecules. Nucleotide modification is one of the improvement strategies.

Studies have shown that nucleotide modification can greatly enhance the functional properties of mRNA by increasing the stability and reducing the immunogenicity of RNA molecules.