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Biocatalytic assembly of chemically modified oligonucleotides

Mann, Greg, Stanger, Frederic, Peschke, Theo, Schroer, Kirsten, Nguyen Trung, Nhat Quang, Burrer, Nathalie, Grassinger, Franziska, Piccioni, Lorenzo, Erdogan, Oemer, Heimburger, Jeremy, Koehl, Herve, Ertle, Heike, Denay, Regis, Dreier, Philippe and Schlama, Thierry (2022) Biocatalytic assembly of chemically modified oligonucleotides. Tetrahedron letters. ISSN 00404039


With renewed interest in therapeutic oligonucleotides, and at the same time the pharmaceutical industry set itself ambitious sustainability goals, there is a strong interest to investigate next-generation synthesis methods for these highly modified oligonucleotides. We herein report an RNA ligase catalyzed assembly of multiple, short oligonucleotides in aqueous solution to generate the potential cardiovascular Blockbuster, Inclisiran. Despite the extensive chemical modifications contained in Inclisiran, a conversion of the non-native substrates to the desired product of 40 – 80 % was achieved.

Item Type: Article
Keywords: Oligonucleotides, Biocatalysis, Sustainable, Ligation
Date Deposited: 22 Mar 2022 00:45
Last Modified: 22 Mar 2022 00:45


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