As the market demand for RNA therapeutics such as siRNA and sgRNA is anticipated to grow substantially over the next decade, there is a need for scalable, cost-effective, and sustainable manufacturing solutions.
Chemoenzymatic ligation is a promising approach for siRNA and sgRNA manufacturing, offering enhanced purity, increased yield, and reduced environmental impact. This innovative technology provides an optimal solution to meet the anticipated surge in demand for these drugs over the coming decade.
At TIDES USA 2025, our CTO, David Butler presented the latest advancements in Hongene’s chemoenzymatic ligation platform for oligonucleotides synthesis and provided strategic insights that will help researchers and companies navigate drug development process using the ligation technology.
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.
Chemoenzymatic ligation is set to transform therapeutic oligonucleotide manufacturing, offering a precise, scalable alternative to traditional solid-phase synthesis (SPOS).
By combining the accuracy of enzymatic reactions with the control of chemical synthesis, this approach supports the production of high-purity oligonucleotides at scale, reducing
costs and minimizing environmental impact.
Whilst this technology can be applied to oligonucleotide constructs generally, it is ideally suited for siRNA and long sgRNA.