Development of a new genotype–phenotype linked antibody screening system

Antibodies are powerful tools for the therapy and diagnosis of various diseases. In addition to conventional hybridoma-based screening, recombinant antibody-based screening has become a common choice; however, its application is hampered by two factors: (1) screening starts after Ig gene cloning and...

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Main Authors: Takashi Watanabe, Hikaru Hata, Yoshiki Mochizuki, Fumie Yokoyama, Tomoko Hasegawa, Naveen Kumar, Tomohiro Kurosaki, Osamu Ohara, Hidehiro Fukuyama
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2024-11-01
Series:eLife
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Online Access:https://elifesciences.org/articles/95346
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author Takashi Watanabe
Hikaru Hata
Yoshiki Mochizuki
Fumie Yokoyama
Tomoko Hasegawa
Naveen Kumar
Tomohiro Kurosaki
Osamu Ohara
Hidehiro Fukuyama
author_facet Takashi Watanabe
Hikaru Hata
Yoshiki Mochizuki
Fumie Yokoyama
Tomoko Hasegawa
Naveen Kumar
Tomohiro Kurosaki
Osamu Ohara
Hidehiro Fukuyama
author_sort Takashi Watanabe
collection DOAJ
description Antibodies are powerful tools for the therapy and diagnosis of various diseases. In addition to conventional hybridoma-based screening, recombinant antibody-based screening has become a common choice; however, its application is hampered by two factors: (1) screening starts after Ig gene cloning and recombinant antibody production only, and (2) the antibody is composed of paired chains, heavy and light, commonly expressed by two independent expression vectors. Here, we introduce a method for the rapid screening of recombinant monoclonal antibodies by establishing a Golden Gate-based dual-expression vector and in-vivo expression of membrane-bound antibodies. Using this system, we demonstrate the rapid isolation of influenza cross-reactive antibodies with high affinity from immunized mice within 7 days. This system is particularly useful for isolating therapeutic or diagnostic antibodies, for example during foreseen pandemics.
format Article
id doaj-art-7c8635ab87ed41a1accabbc80ff78a36
institution Kabale University
issn 2050-084X
language English
publishDate 2024-11-01
publisher eLife Sciences Publications Ltd
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series eLife
spelling doaj-art-7c8635ab87ed41a1accabbc80ff78a362024-11-19T07:30:23ZengeLife Sciences Publications LtdeLife2050-084X2024-11-011310.7554/eLife.95346Development of a new genotype–phenotype linked antibody screening systemTakashi Watanabe0https://orcid.org/0000-0002-6184-0375Hikaru Hata1Yoshiki Mochizuki2Fumie Yokoyama3Tomoko Hasegawa4Naveen Kumar5Tomohiro Kurosaki6Osamu Ohara7https://orcid.org/0000-0002-3328-9571Hidehiro Fukuyama8https://orcid.org/0000-0002-6457-0630Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanLaboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanLaboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanLaboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanLaboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanLaboratory for Integrated Bioinformatics, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanLaboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, JapanLaboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Applied Genomics, Kazusa DNA Research Institute, Chiba, JapanLaboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Immunology, Near-InfraRed Photo-Immunotherapy Research Institute, Kansai Medical University, Osaka, Japan; INSERM EST, Strasbourg Cedex, FranceAntibodies are powerful tools for the therapy and diagnosis of various diseases. In addition to conventional hybridoma-based screening, recombinant antibody-based screening has become a common choice; however, its application is hampered by two factors: (1) screening starts after Ig gene cloning and recombinant antibody production only, and (2) the antibody is composed of paired chains, heavy and light, commonly expressed by two independent expression vectors. Here, we introduce a method for the rapid screening of recombinant monoclonal antibodies by establishing a Golden Gate-based dual-expression vector and in-vivo expression of membrane-bound antibodies. Using this system, we demonstrate the rapid isolation of influenza cross-reactive antibodies with high affinity from immunized mice within 7 days. This system is particularly useful for isolating therapeutic or diagnostic antibodies, for example during foreseen pandemics.https://elifesciences.org/articles/95346membrane-bound Ig expressionngs-based Ig-seqgolden gate cloninginfluenza broadly-reactive
spellingShingle Takashi Watanabe
Hikaru Hata
Yoshiki Mochizuki
Fumie Yokoyama
Tomoko Hasegawa
Naveen Kumar
Tomohiro Kurosaki
Osamu Ohara
Hidehiro Fukuyama
Development of a new genotype–phenotype linked antibody screening system
eLife
membrane-bound Ig expression
ngs-based Ig-seq
golden gate cloning
influenza broadly-reactive
title Development of a new genotype–phenotype linked antibody screening system
title_full Development of a new genotype–phenotype linked antibody screening system
title_fullStr Development of a new genotype–phenotype linked antibody screening system
title_full_unstemmed Development of a new genotype–phenotype linked antibody screening system
title_short Development of a new genotype–phenotype linked antibody screening system
title_sort development of a new genotype phenotype linked antibody screening system
topic membrane-bound Ig expression
ngs-based Ig-seq
golden gate cloning
influenza broadly-reactive
url https://elifesciences.org/articles/95346
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