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3'-Modification stabilizes mRNA and increases translation in cells.
Bioorganic & Medicinal Chemistry Letters 2018 August 2
Successful implementation of mRNA gene therapy is facing many hurdles, for example poor expression levels of the exogenously delivered mRNA transcripts. Herein we describe the synthesis of various 3'-modified RNA oligonucleotides, and we show that 3'-modification drastically stabilizes these oligonucleotides in cell extracts. Modification of the 3'-terminus of gaussia luciferase mRNA results in 3-fold increased and extended (>48 h) translation of the mRNA. Our findings suggest 3'-modification of RNA-transcripts as a valid approach to increase expression levels for application in mRNA gene therapy.
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