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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 (antibody-like), 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. 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. LICHEN can thus be used across multiple antibody engineering scenarios for efficient light-chain pairing.<\/jats:p>","DOI":"10.1038\/s42003-026-09727-3","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T11:06:00Z","timestamp":1771671960000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["LICHEN enables light-chain immunoglobulin sequence generation conditioned on the heavy chain and experimental needs"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3757-5313","authenticated-orcid":false,"given":"Henriette L.","family":"Capel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5556-2965","authenticated-orcid":false,"given":"Isaac","family":"Ellmen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Mignone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Black","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"Breen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Tierney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Dougan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Buick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8740-9823","authenticated-orcid":false,"given":"Alexander","family":"Greenshields-Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1388-2252","authenticated-orcid":false,"given":"Charlotte M.","family":"Deane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,21]]},"reference":[{"key":"9727_CR1","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s42003-023-05744-8","volume":"7","author":"MI Raybould","year":"2024","unstructured":"Raybould, M. 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C.J.M., G.M., M.B., B.C., C.B., S.T., and P.D. were employed by Fusion Antibodies plc. C.M.D. discloses membership of the Scientific Advisory Board of Fusion Antibodies plc and AI proteins, and is a founder of DaltonTx. All other authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"468"}}