An enzyme cascade enables production of therapeutic oligonucleotides in a single operation.
- Resource Type
- Article
- Authors
- Moody, E. R.; Obexer, R.; Nickl, F.; Spiess, R.; Lovelock, S. L.,
- Source
- Science; 6/16/2023, Vol. 380 Issue 6650, p1150-1154, 5p, 5 Color Photographs
- Subject
- Oligonucleotides
Polymerases
Enzymes
Endonucleases
Scalability
Sustainability
- Language
- ISSN
- 00368075
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. [ABSTRACT FROM AUTHOR]