Resources
Presentation
As several siRNA therapeutics move toward regulatory approval for cardiometabolic diseases, we expect demand for large-scale manufacturing to grow sharply over the coming decade.
At TIDES Europe 2025 in Basel, our CTO, David Butler, spoke about the limitations of traditional solid-phase oligonucleotide synthesis in meeting that demand at the scale, cost, and level of sustainability the field will require.
The presentation focused on chemoenzymatic ligation, a next-generation manufacturing approach for producing high-purity siRNA more efficiently at a larger scale. Two case studies demonstrated how this approach can 1) support complex formats such as multivalent siRNAs, and 2) reduce manufacturing costs by eliminating chromatography from the process.
Dave highlighted the importance of engineered thermostable ligases in improving process performance and enabling future scale-up. In addition, he covered key CMC and regulatory considerations for bringing this technology into clinical development, including the exciting recent announcement that we have completed cGMP manufacturing of a GalNAc-siRNA conjugate targeting PCSK9 for use in human dosing.
David Butler
Chief Technology Officer
David Butler, Chief Technology Officer, has nearly two decades of experience in the oligonucleotide field. Prior to joining Hongene in 2023, he led organizations driving drug discovery and development of oligonucleotide therapeutics, most recently as Head of Chemistry at Korro Bio, Head of Therapeutics Development at Alltrna, and Head of Medicinal Chemistry at Wave Life Sciences. He began his career in oligonucleotides as a Principal Scientist at Alnylam Pharmaceuticals in 2007 developing early LNP technologies for siRNA delivery that were the progenitors of those used for mRNA related products today. He holds a PhD in Chemistry from the University of St Andrews, and is passionate about working with individuals and companies to help them succeed.