Identification of cross-reactive single-domain antibodies against serum albumin using next-generation DNA sequencing

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DOIResolve DOI: http://doi.org/10.1093/protein/gzv039
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TypeArticle
Journal titleProtein Engineering, Design and Selection
ISSN1741-0126
1741-0134
Volume28
Issue10
Pages379383; # of pages: 5
Subjectnext-generation DNA sequencing; phage display; serum albumin; single-domain antibody; VHH
AbstractAntibodies that cross-react with multiple isoforms or homologue of a given protein are often desirable, especially in therapeutic applications. Here, we report the identification of several unique, clonally unrelated, single-domain antibodies (sdAbs) that bind to multiple serum albumin orthologues (human, rhesus, rat and mouse) with low-to-medium nanomolar affinity from a llama immunized only with human serum albumin. Using single-round panning of a phage-displayed sdAb library against serum albumins and next-generation DNA sequencing, we were able to predict patterns of sdAb reactivity to the albumins of different species with ∼90% accuracy. We expect this strategy to be generally applicable for identifying cross-reactive sdAbs, particularly when these exist at low frequency and/or are poorly enriched by panning. Moreover, the sdAbs identified here are of potential interest for serum half-life extension of biologics.
Publication date
PublisherOxford University Press
LanguageEnglish
AffiliationNational Research Council Canada; Human Health Therapeutics
Peer reviewedYes
NRC numberNRC-HHT-53302
NPARC number21277516
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Record identifier0526bdcc-d6b2-430e-b9e9-4e9e5edcd6d8
Record created2016-03-10
Record modified2016-05-09
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