Home / Small molecules / Integrated Services / Process Enabling Technologies (TIDES)
Peptide and Oligonucleotide Process Enabling Technologies
The synthesis and purification platforms behind every peptide and oligonucleotide we make — sized for commercial supply, available while your sequence is still changing.
Scale is the question for peptides and oligonucleotides
A peptide or oligonucleotide that works in a discovery lab is not yet a manufacturable molecule. The chemistry is the same at 100 mg and at 100 kg, but the process is not: coupling efficiency that is acceptable over twenty residues compounds into an impurity profile that is not, solvent volumes that were trivial become the dominant cost, and purification moves from a column to a plant.
The four platforms below close that gap, and they are available from discovery onward because the sequence decisions that determine whether a molecule can be made at scale are taken before a process exists.
Solid-phase synthesis
Solid-phase synthesis is the backbone of both modalities, and installed reactor capacity is the measure of it.
For peptides, WuXi TIDES has more than twenty Solid Phase Peptide Synthesis (SPPS) production lines with vessels from 10 liters to 5,000 liters, for a total reactor volume above 137,000 liters across eight plants. On the oligonucleotide side, around thirty manufacturing lines, including four large-scale OligoProcess systems at Changzhou, at a total reactor scale above 8 moles. Two further plants are under construction at Taixing for 2027 and one at Singapore for the second quarter of 2028.
The vessel range matters more than the total. A process that has to jump from a 50 L pilot straight to a 3,000 L campaign carries risk that a process moving through intermediate scales does not. Every intermediate scale is available on one site, running the same analytical methods, which keeps scale-up an engineering question.
Liquid-phase synthesis
Solid-phase is not always the right answer. Where a sequence is long, heavily modified or structurally difficult, a hybrid approach, assembling most of the sequence on resin and taking the difficult portion into solution, often gives better economics and a cleaner impurity profile than either method alone.
Liquid-phase peptide synthesis and liquid-phase oligonucleotide synthesis both run at WuXi TIDES, and the decision is made per molecule. For peptides, hybrid solid- and liquid-phase routes are applied to long sequences, modified peptides and complex structures. For oligonucleotides, LPOS sits alongside solid-phase and ligation-enabled routes as one of three manufacturing modes selected on the basis of the sequence.
Continuous flow chromatography
Purification is where peptide and oligonucleotide process economics are decided. Batch preparative chromatography puts a hard limit on throughput and consumes solvent in proportion to the material it fails to recover. Continuous flow chromatography recycles the fractions that batch discards, which raises yield and cuts solvent at the same time.
The result shows in process mass intensity. Our commercial peptide API manufacture runs at a PMI per amino acid of 85, against a published industry average of 875, a factor of ten in material consumed per unit of product.
Continuous flow chromatography runs on both platforms, alongside ion-exchange, reverse-phase, hydrophobic interaction and membrane-enabled purification for oligonucleotides, and ion-exchange and reverse-phase for peptides. The method is chosen per molecule, and for a difficult separation the answer is often a combination rather than one technique.
Fragment ligation
Long sequences are the practical ceiling on both modalities. Stepwise synthesis accumulates deletion and truncation impurities with every residue, and past a certain length the purification burden overtakes the synthesis. Ligation strategies address that by making fragments separately and joining them.
For oligonucleotides, the route is enzymatic. Ligase-enabled strategies support long RNA constructs in the 60 to 158 mer range and circular RNA, and biocatalysis is used for guide RNA synthesis. Enzymatic ligation also appears in manufacturing as one of the process options introduced selectively as scale increases, alongside PN bond formation, precipitation, stirred-bed processing and thin-film evaporation.
For peptides, the route is chemical. Native chemical ligation supports sequences up to 150 amino acids, with KAHA ligation available where the junction does not suit a cysteine-based approach. Ring-closing metathesis and click chemistry sit in the same toolkit for the cyclization problems that often accompany long sequences.
Enzymatic and chemical ligation are different chemistries solving the same problem, and the choice depends on the sequence. Past a certain length, making the molecule in two pieces and joining them gives a cleaner product than making it in one.
Choosing between the routes
For a long or heavily modified sequence, the choice between solid-phase, liquid-phase, hybrid and ligation routes is the single largest lever on cost of goods, and it is made once.
All four routes run at WuXi TIDES, so the recommendation is made on the sequence.