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

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1093/protein/gzv039
AuthorSearch for: 1; Search for: 1; Search for: 1
Name affiliation
  1. National Research Council of Canada. Human Health Therapeutics
FormatText, Article
Journal titleProtein Engineering, Design and Selection
ISSN1741-0126
1741-0134
Volume28
Issue10
Pages379–383
Subjectnext-generation DNA sequencing; phage display; serum albumin; single-domain antibody; VHH
Abstract
Antibodies 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
Peer reviewedYes
NRC numberNRC-HHT-53302
NPARC number21277516
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Record modified2020-04-22
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