The unique dinucleotide cap structure, m7G[5']ppp[5']N (where N = G, A, C or U) in which 7-methylguanosine residue is connected to the 5'-end of the transcribed RNA via a 5'-5' bridge is present at the 5'-end of many eukaryotic cellular and viral RNAs.1-3 Unlike synthetic standard cap, m7G[5′]ppp[5′]G, the use of anti-reverse cap analog (ARCA) incorporates exclusively in the forward orientation due to the chemical modifications at 3′-OH or 2′-OH group on m7G moiety. Currently, Thermo Fisher Scientific has been selling mMessage mMachineTM kits that contain ARCA which support innovations to our customers in the areas of RNA-based vaccines and therapeutics, cancer immunotherapy, protein production, and gene therapy. The effect of chemical modifications on cap analogs has had a huge impact on the translational efficiency, binding properties, and nuclear stability. In this line, we have designed and synthesized several cap analogs containing 2′-F, 2′,3′-isopropylidene, LNA, 2′-(ara)-F, 2′-allyl, and 3′-propargyl modifications and evaluated their molecular biology applications. Full details of the design, synthesis, and molecular biology results will be presented.

Overview of dinucleotide mRNA cap analogues: Design, synthesis, and biological evolution towards mRNA therapeutics

2019 Spring National Meeting

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