Upcoming Drugs: In Vivo Gene Transfer With Messenger RNA

Dear all,

the world of nucleic acid therapeutics is fascinating. A novel advancement in this field develops messenger RNA as a tool for in vivo gene transfer, either for antigen expression in vaccination procedures, or to improve, and even supplement homologous gene expression for disease treatment. It is obvious the messenger RNA has to be chemically stabilized somehow, in order to suppress or at least to delay in vivo degradation.
There are several ways to achieve this goal: modifications of the ribose backbone are already in the clinic (with the great disadvantage this modification can hardly be incorporated into the GMP manufacturing process by in vitro transcription). The use of naturally occuring nucleosides like pseudouridine (1), 2-thiouridine (2), or 5-methylcytidine is a promising approach to produce large amounts of biologically stabilized in vitro transcripts enzymatically. The 5-methylcytidine modification is that “famous” methylation of genomic DNA for pre-transcriptional gene silencing (monoclonal antibodies to this modification are used in immunoprecipitation of genomic DNA).
Another approach uses no chemical modification at all, but the in vitro transcripts are complexed with the cationic peptide protamine (3). Both components form a complex which improves biological stability of the messenger RNA in vivo, but on the other hand represses translation of the messenger RNA. Read our latest summary on novel and innovative messenger RNA therapeutics.

Enjoy your weekend, your binding-assay.com team.

(1) Karikó K et al (2008), Mol Ther 16(11): 1833-40.
(2) Kormann MSD et al (2011), Nature Biotech 29(2): 154-7.
(3) Scheel B et al (2005), Eur J Immunol 35: 1557-66.

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