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 meth...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.展开更多
文摘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.
