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Chemoenzymatic ligation comes of age: A present-day solution for scalable manufacturing for siRNA and sgRNA drugs
May 18, 2025

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

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 Brochure

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.