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Conjugation and Bioconjugates
The payload, the linker and the sequence, made in one organization.
What a conjugate program has to source
A conjugate program rarely runs late because the conjugation chemistry fails. More often the peptide comes from one supplier, the toxin or chelator from a second and the linker from a third, and each handover brings a new set of analytical methods, a new impurity discussion and a shipment waiting on customs.
We make all three: small molecule chemistry, peptide synthesis and oligonucleotide synthesis are one organization at WuXi, so the conjugation step can be developed while the components are still being optimized.
Oligonucleotide-based conjugates
GalNAc, lipid, cholesterol, peptide and other linker-enabled conjugates, attached at the 3′ or the 5′ end. Conjugation runs either after synthesis, by amide bond formation or click chemistry including post-UF/DF workflows, or during solid-phase assembly itself, using amidite-based 5′ modification or custom-loaded supports for 3′ attachment.
Building the conjugation into the assembly means different designs can be evaluated without reworking the synthesis route each time, so several linker geometries can be tested in one campaign.
For liver-targeted work, GalNAc is made in-house: more than 100 types including mono-, tri- and tetra-GalNAc, GalNAc amidite, PFP ester, azide and PEG conjugates. Purification of conjugated oligonucleotides uses ion-exchange, ion-pair and tangential flow filtration to clear unconjugated species and linker-related impurities.
Peptide-oligonucleotide conjugates and PPMO
Eighteen of the conjugates we support are peptide-oligonucleotide, including peptide-PMO (phosphorodiamidate morpholino oligomer). The class needs a peptide platform and an oligonucleotide platform on one site with a shared analytical group.
We have completed dozens of PMO projects, more than 10 of them PPMO (peptide-conjugated PMO), with the work sited at Changzhou where both platforms and the conjugation chemistry sit together.
Peptide-based conjugates
Peptide-drug, peptide-lipid, radionuclide-drug and other ligand- or payload-modified peptides, drawing on more than 1,600 linkers and a payload library that includes toxins, chelators, GalNAc and radionuclide handles. More than 360 peptides, lipids, and PEG linkers are available off the shelf for early conjugation work.
Design decisions made with scale-up in view
The linker chemistry that works on 50 mg does not always work on 5 kg, and the conjugation strategy chosen in discovery is usually the one carried to IND. Because process development runs in the same organization, scale-up feasibility can be assessed while several leads are still open.