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TitleGeneration of antigen-specific paired-chain antibodies using large language models.
Journal, issue, pagesCell, Vol. 188, Issue 25, Page 7206-7221.e16, Year 2025
Publish dateDec 11, 2025
AuthorsPerry T Wasdin / Nicole V Johnson / Alexis K Janke / Sofia Held / Toma M Marinov / Gwen Jordaan / Rebecca A Gillespie / Léna Vandenabeele / Fani Pantouli / Olivia C Powers / Matthew J Vukovich / Clinton M Holt / Jeongryeol Kim / Grant Hansman / Jennifer Logue / Helen Y Chu / Sarah F Andrews / Masaru Kanekiyo / Giuseppe A Sautto / Ted M Ross / Daniel J Sheward / Jason S McLellan / Alexandra A Abu-Shmais / Ivelin S Georgiev /
PubMed AbstractThe traditional process of antibody discovery is limited by inefficiency, high costs, and low success rates. Recent approaches employing artificial intelligence (AI) have been developed to optimize ...The traditional process of antibody discovery is limited by inefficiency, high costs, and low success rates. Recent approaches employing artificial intelligence (AI) have been developed to optimize existing antibodies and generate antibody sequences in a target-agnostic manner. In this work, we present MAGE (monoclonal antibody generator), a sequence-based protein language model (PLM) fine-tuned for the task of generating paired human variable heavy- and light-chain antibody sequences against targets of interest. We show that MAGE can generate novel and diverse antibody sequences with experimentally validated binding specificity against SARS-CoV-2, an emerging avian influenza H5N1, and respiratory syncytial virus A (RSV-A). MAGE represents a first-in-class model capable of designing human antibodies against multiple targets with no starting template.
External linksCell / PubMed:41192421 / PubMed Central
MethodsEM (single particle)
Resolution3.4 Å
Structure data

48331

9mkn

EMDB-48331, PDB-9mkn:
Structure of the Respiratory Syncytial Virus Fusion Protein Bound to Human Antibodies RSV_2245 and RSV_3301
Method: EM (single particle) / Resolution: 3.4 Å

Source
  • homo sapiens (human)
  • respiratory syncytial virus
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / fusion protein / trimer / antibody / complex / ANTIVIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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