Self-amplifying RNA generated with the modified nucleotides 5-methylcytidine and 5-methyluridine mediate strong expression and immunogenicity in vivo

When utilized in therapeutic applications, synthetic self-amplifying RNA can lead to higher and more sustained expression than standard messenger RNA. This feature is particularly important for gene replacement therapy applications where prolonged expression could reduce the dose and frequency of treatments. The inclusion of modified nucleotides in synthetic non-amplifying mRNA has been shown to increase RNA stability, reduce immune activation and enhance gene expression. Preclinical and clinical studies with self-amplifying RNA (saRNA) have so far exclusively relied on RNA containing the canonical nucleotides adenosine, cytidine, guanosine and uridine. For the first time, we show that non-canonical nucleotides, such as m5C and m5U, are sufficiently compatible with a replicon derived from Venezuelan equine encephalitis alphavirus mediating protein translation in vitro, while those containing m1ψ in place of uridine show no detectable expression. When administered in vivo, saRNA generate..., , , # Data from: Self-amplifying RNA generated with the modified nucleotides 5-methylcytidine and 5-methyluridine mediate strong expression and immunogenicity in vivo

This README.md file was generated on 2024-04-05 by Bassel Akache & Tyler Renner.

GENERAL INFORMATION

1. Title of Dataset: Self-Amplifying RNA Generated with the Modified Nucleotides 5-MethylCytidine and 5-MethylUridine Mediate Strong Expression & Immunogenicity in vivo

Related Article of the same title submitted to Nucleic Acids Research Molecular Medicine.

2. Author information:

Hiva Azizi1, Tyler M. Renner1, Gerard Agbayani1, Bryan Simard1, Renu Dudani1, Blair A. Harrison1, Umar Iqbal1, Yimei Jia1, Michael J. McCluskie1 and Bassel Akache1*

1National Research Council Canada, Human Health Therapeutics, Ottawa, Ontario, Canada, K1A 0R6

* To whom correspondence should be addressed: Bassel Akache, Email: [[e-mail]](mailto:[e-mail])

3. Date of data colle...