RNA Codon Exchange for Reduced Immunogenicity

The patent changes the nucleoside composition parameters of RNA molecules by reducing cytidine and uridine content and replacing them with adenosine and guanosine. This parameter change reduces immunogenicity while maintaining translation fidelity, as demonstrated by the reduced cytokine release and maintained protein expression levels in the patent data.

The patent creates simplified RNA molecules that copy only the essential functional elements of natural RNA while eliminating immunogenic components. By using only adenosine and guanosine nucleosides, the patent produces RNA that replicates protein translation function without triggering immune responses.

The patent fundamentally changes the nucleoside composition parameters of therapeutic RNA to reduce immunogenicity. This allows administration of higher RNA doses to achieve therapeutic protein levels without proportionally increasing immune activation, as the modified RNA composition decouples dose from immune response intensity.

The patent converts the harmful effect of high RNA dosing (immune activation) into a benefit by modifying nucleoside composition. The reduced immunogenicity of adenosine-guanosine-rich RNA transforms what would be a toxic high-dose scenario into a safe and effective therapeutic approach.

The patent uses simple, naturally occurring adenosine and guanosine nucleosides instead of complex chemically modified nucleosides. These simple building blocks maintain natural RNA structure and function while providing the immunogenicity reduction benefit, avoiding the structural disruption caused by chemical modifications.

The patent changes the nucleoside composition by reducing cytidine and uridine content while maintaining RNA structure stability. The resulting adenosine-guanosine-rich RNA maintains proper secondary structures and tRNA binding properties, as evidenced by successful protein translation in the patent data.