An enzyme cascade enables production of therapeutic oligonucleotides in a single operation.

Science

Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, Manchester, UK.

Published: June 2023

Therapeutic oligonucleotides have emerged as a powerful drug modality with the potential to treat a wide range of diseases; however, the rising number of therapies poses a manufacturing challenge. Existing synthetic methods use stepwise extension of sequences immobilized on solid supports and are limited by their scalability and sustainability. We report a biocatalytic approach to efficiently produce oligonucleotides in a single operation where polymerases and endonucleases work in synergy to amplify complementary sequences embedded within catalytic self-priming templates. This approach uses unprotected building blocks and aqueous conditions. We demonstrate the versatility of this methodology through the synthesis of clinically relevant oligonucleotide sequences containing diverse modifications.

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Source
http://dx.doi.org/10.1126/science.add5892DOI Listing

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