"Introduction: ... Aside from the delivery problem discussed above, therapeutic mRNA had at least two additional big challenges: 1) the in vitro transcribed (IVT) mRNA would be prone to nuclease degradation when injected into animals, and 2) the IVT mRNA would also lead to innate immunogenicity similar to what would happen when infected by a pathogen (Martinon et al., 1993; Hoerr et al., 2000). The answer to these problems came from a well-known RNA modification, pseudouridine (Ψ), which can be used to replace uridine in the IVT mRNA. It is demonstrated that Ψ can enhance RNA stability and, in the meantime, decrease anti-RNA immune response (Karikó et al., 2008)."
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