As several siRNA assets indicated for treating diseases associated with cardiovascular targets advance toward potential approval, the market demand for high-quality oligonucleotides is anticipated to grow substantially over the next decade. Gene editing drugs are also emerging as a viable modality to treat human disease and there is a growing need for increasingly long sgRNA oligonucleotides with high purity.
The current method for oligonucleotide production relies completely on solid-phase synthesis using the phosphoramidite method and encounters challenges related to scalability, product purity, and environmental sustainability.
Chemoenzymatic ligation technology offers the promise of improved purity, yield, and environmental sustainability. It is particularly well-suited for large-scale production of siRNA and high-purity synthesis of sgRNA, making it an optimal solution for meeting future market demands.
In this video, our CTO David Butler, explores the challenges and ongoing innovation in scaling oligonucleotide production to meet an expected exponential growth in demand for RNA therapeutics over the next decade, focusing on ligation technology applied to siRNA and long sgRNA molecules.
David Butler
最高技術責任者（CTO）
David Butler は、オリゴヌクレオチド分野で約 20 年の経験を持つ専門家です。2023 年に Hongene に入社する前は、Korro Bio の化学部門責任者、Alltrna の治療薬開発部門責任者、Wave Life Sciences の創薬化学部門責任者として、オリゴヌクレオチド治療薬の発見と開発を推進してきました。彼は 2007 年に Alnylam Pharmaceuticals の主任科学者としてキャリアをスタートし、siRNA デリバリーの初期 LNP 技術を開発しました。この技術は現在の mRNA 関連製品に使用されているものの先駆けとなりました。彼はセントアンドリューズ大学で化学の博士号を取得し、個人や企業の成功を支援することに情熱を持っています。
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.
