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3′-Modification stabilizes mRNA and increases translation in cells

Gampe, Christian and White, Amy and Siva, Swetha and Zecri, Frederic and Diener, John (2018) 3′-Modification stabilizes mRNA and increases translation in cells. Bioorganic and Medicinal Chemistry Letters. ISSN 1464-3405

Abstract

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.

Item Type: Article
Keywords: 3′-Terminus Bioconjugation Gene therapy mRNA Nucleotide Translation
Date Deposited: 04 Jul 2018 00:45
Last Modified: 25 Jan 2019 00:45
URI: https://oak.novartis.com/id/eprint/35939

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