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Bachem releases whitepaper on enzymatic ligation in oligonucleotide manufacturing

white-paperBachem AG
February 10th 2026

Leading CDMO Bachem has produced a whitepaper that explains how innovative synthesis methods have the potential to revolutionize the large-scale production  of the oligonucleotides that power a wide range of NextGen therapies.

Oligomer-based therapeutics are transforming modern medicine, offering targeted solutions for genetic disorders, cancer, cardiovascular disease, and CNS conditions. With more than 700 oligonucleotide drugs in the global pipeline and demand for large-scale production growing rapidly, the need for commercial scale manufacturing has become a critical priority for pharma companies.

Impact of Process Innovation

The Bachem technical bulletin ‘Enzymatic Ligation and Other Innovative Technologies: Shaping the Future of Large-Scale Oligonucleotide Manufacturing’ is available for immediate reading online or download.

It explains how traditional synthesis methods founded in peptide production can present challenges when applied to longer, chemically complex sequences in oligo production: particularly regarding yield, scalability, and environmental sustainability.

The whitepaper shows how innovative approaches such as fragment synthesis and enzymatic ligation can overcome such challenges to deliver higher efficiency, greener processes, and greater flexibility in production.

New Solid and Liquid Phase approaches

The bulletin explores the role of fragment synthesis with other innovations such as Stirred Bed Technology (SBT SPOS), and Tag-Assisted One-Pot Liquid Phase Oligonucleotide Synthesis (TOP LPOS) in enabling large-scale, sustainable manufacturing.

It shows how these can be applied across  range of common applications, including siRNA, oligonucleotide conjugates, and complex molecular structures.

Efficiency and Sustainability

Specifically, the white paper explains how enzymatic ligation can improve cost efficiency, reduce chemical waste, and support greener production processes, with Bachem’s enzymatic ligation processes now routinely achieving >90–95% purity and higher overall yields.

It also details Bachem’s proven expertise and progress in scaling oligonucleotide manufacturing from gram to multi-kilogram in GMP production.

The latest guide adds to a suite of Bachem scientific tools, including the Online Peptide Guide for Beginners, a Peptide Calculator, Peptide Content Calculator, Oligo Calculator, and a series of peptide-related blogs, webinars, and technical papers.

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