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2 results for “Modified nucleotides”
Data from: Self-amplifying RNA generated with the modified nucleotides 5-methylcytidine and 5-methyluridine mediate strong expression and immunogenicity in vivo
<p>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 <em>in vitro</em>, while those containing m1ψ in place of uridine show no detectable expression. When administered <em>in vivo</em>, saRNA generated with m5C or m5U mediate sustained gene expression of the luciferase reporter gene with those incorporating m5U appearing to lead to more prolonged expression. Finally, distinct antigen-specific humoral and cellular immune responses were induced by modified saRNA encoding the model antigen ovalbumin. The use of modified nucleotides with saRNA-based platforms could enhance their potential to be used effectively in a variety of applications.</p>
Data from: Self-amplifying RNA generated with the modified nucleotides 5-methylcytidine and 5-methyluridine mediate strong expression and immunogenicity in vivo
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