LICHEN: Light-chain Immunoglobulin sequence generation Conditioned on the Heavy chain and Experimental Needs

Capel, H. L.; Ellmen, I.; Murray, C. J.; Mignone, G.; Black, M.; Clarke, B.; Breen, C.; Tierney, S.; Dougan, P.; Buick, R. J.; Greenshields-Watson, A.; Deane, C. M.

doi:10.1101/2025.08.06.668938

bioRxiv · 10.1101/2025.08.06.668938

LICHEN: Light-chain Immunoglobulin sequence generation Conditioned on the Heavy chain and Experimental Needs

Capel, H. L.·Ellmen, I.·Murray, C. J.·Mignone, G.·Black, M.·Clarke, B.·Breen, C.·Tierney, S.·Dougan, P.·Buick, R. J.·Greenshields-Watson, A.·Deane, C. M.

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Abstract

In developing therapeutic antibodies, the heavy chain is often prioritised due to its higher variability and its central role in antigen binding. An appropriate pairing of the light sequence is however important for antibody function. Here we present LICHEN, a heavy chain conditioned light sequence generation tool that enables collaborative light sequence design by leveraging computational capabilities alongside experimental expertise. LICHEN generates light sequences which are valid (antibodylike), diverse in sequence and structure, and conditioned on a specific heavy chain. LICHEN can also condition on germline and CDRs and automatically filter generated sequences for required properties. This allows LICHEN to be used across multiple antibody development use cases. We carry out experimental validation of the method conditioning only on the heavy sequence and on the heavy sequence and binding information. Our in vitro results show that sequences created by LICHEN have effective expression yields and can retain antigen-binding.

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Capel, H. L., Ellmen, I., Murray, C. J., Mignone, G., Black, M., Clarke, B., Breen, C., Tierney, S., Dougan, P., Buick, R. J., Greenshields-Watson, A., Deane, C. M.. 2025-08-07. LICHEN: Light-chain Immunoglobulin sequence generation Conditioned on the Heavy chain and Experimental Needs. https://doi.org/10.1101/2025.08.06.668938

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