A Sortase A Programmable Phage Display Format for Improved Panning of Fab Antibody Libraries.

J Mol Biol

Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL 33458, USA. Electronic address:

Published: October 2018


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Article Abstract

Phage display of combinatorial antibody libraries is a versatile tool in the field of antibody engineering, with diverse applications including monoclonal antibody (mAb) discovery, affinity maturation, and humanization. To improve the selection efficiency of antibody libraries, we developed a new phagemid display system that addresses the complication of bald phage propagation. The phagemid facilitates the biotinylation of fragment of antigen binding (Fab) antibody fragments displayed on phage via Sortase A catalysis and the subsequent enrichment of Fab-displaying phage during selections. In multiple contexts, this selection approach improved the enrichment of target-reactive mAbs by depleting background phage. Panels of cancer cell line-reactive mAbs with high diversity and specificity were isolated from a naïve chimeric rabbit/human Fab library using this approach, highlighting its potential to accelerate antibody engineering efforts and to empower concerted antibody drug and target discovery.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186506PMC
http://dx.doi.org/10.1016/j.jmb.2018.09.003DOI Listing

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