Synthetic messenger RNA (mRNA) can be used to deliver exogenous genetic information inside cells that is converted by the cellular translational machinery into the encoded protein which subsequently induces a cellular response depending on its biological function.
Therapeutic protein encoding mRNAs have most recently gained increasing attention as versatile protein delivery molecules in non-viral gene therapy mostly due to their superior safety profile compared to plasmid DNA-based approaches (inability to integrate into the host genome)
. In addition, high-purity mRNA is easily synthesized even large scales by phage RNA polymerase-mediated in vitro
Their application however, was so far been hampered by the limited stability and strong immunogenicity of in vitro
transcribed mRNAs subsequently leading to increased expression rates of the respective protein.
Enzymatic incorporation of a set several nucleotide analogs (single or combined) during the transcription process markedly improves the pharmacokinetic properties of in vitro
transcribed mRNA both in terms of stability (increased nuclease resistance) and decreased immunogenicity (Fig. 1)[4-8]
Find more Cap analogs in the 5'-Capping