Dr Sarah Lovelock - University of Manchester

Biocatalytic Approaches to Nucleic Acid Therapeutics Manufacturing

Therapeutic oligonucleotides are a powerful drug modality with the potential to treat a wide range of diseases. The rapidly growing number of therapies approved and in advanced clinical trials is placing unprecedented demands on our capacity to manufacture oligonucleotides at scale. Existing methods of chemical synthesis rely on iterative coupling, capping, oxidation and deprotection to achieve stepwise extension of sequences immobilized on solid supports and are limited by their scalability and sustainability. This talk will describe biocatalytic approaches to efficiently produce oligonucleotides in a single operation, where polymerases and endonucleases work in synergy to amplify catalytic self-priming templates. This approach has been used to produce diverse oligonucleotide sequences containing a range of pharmaceutically relevant modifications.