Reliable repurposing of the antibody interactome inside the cell
1
Issued Date
2026-01-31
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-105032229719
Pubmed ID
41620420
Journal Title
Nature Communications
Volume
17
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.17 No.1 (2026)
Suggested Citation
O'Shea C.M., Shahzad R., Aghasoleimani K., Newman S., Panmanee J., Schalkwyk L.C., Brooke G.N., Benson F.E., Trimmer J.S., Bosco D.A., Fujisawa T., Ichijo H., Cashman N.R., Engel S., Wright G.S.A. Reliable repurposing of the antibody interactome inside the cell. Nature Communications Vol.17 No.1 (2026). doi:10.1038/s41467-026-69057-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115741
Title
Reliable repurposing of the antibody interactome inside the cell
Author's Affiliation
The University of Tokyo
Institute of Science Tokyo
Ben-Gurion University of the Negev
University of Massachusetts Chan Medical School
UC Davis School of Medicine
University of Essex
Djavad Mowafaghian Centre for Brain Health
Institute of Molecular Biosciences, Mahidol University
Division of Biomedical and Life Sciences, Lancaster University
Institute of Science Tokyo
Ben-Gurion University of the Negev
University of Massachusetts Chan Medical School
UC Davis School of Medicine
University of Essex
Djavad Mowafaghian Centre for Brain Health
Institute of Molecular Biosciences, Mahidol University
Division of Biomedical and Life Sciences, Lancaster University
Corresponding Author(s)
Other Contributor(s)
Abstract
Eighty-five percent of the human proteome has at least one interacting monoclonal antibody. These molecules penetrate the cytoplasm poorly and are very often non-functional within the cell. Analysis of antibody variable domains and characterisation of forty-five single-chain variable fragment (scFv) intrabodies expressed in human cells indicated charge to have the greatest impact on solubility. We created new interdomain linkers, optimised scFv domain orientation and found an optimisable charge discrepancy between variable heavy framework and CDR sites. When applied to reduce the search space and rank the products of AI-led inverse folding this creates a single highly soluble, abundant and stable intrabody with parent antibody epitope recognition. Over six hundred intrabody sequences are presented targeting sixty cytoplasmic proteins with linear, conformational, post-translational modification or oligomer specificity. Interactions were validated for p53, α-synuclein, SOD1, polyQ, FUS/TLS, UCHL1 and GFP. Here we show reliable repurposing of the sequenced antibody interactome inside the cell.