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Generation of nanobodies from transgenic 'LamaMice' lacking an endogenous immunoglobulin repertoire

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Generation of nanobodies from transgenic 'LamaMice' lacking an endogenous immunoglobulin repertoire. / Eden, Thomas; Schaffrath, Alessa Z; Wesolowski, Janusz; Stähler, Tobias; Tode, Natalie; Richter, Nathalie; Schäfer, Waldemar; Hambach, Julia; Hermans-Borgmeyer, Irm; Woens, Jannis; Le Gall, Camille M; Wendler, Sabrina; Linke-Winnebeck, Christian; Stobbe, Martina; Budnicki, Iwona; Wanney, Amelie; Heitz, Yannic; Schimmelpfennig, Lena; Schweitzer, Laura; Zimmer, Dennis; Stahl, Erik; Seyfried, Fabienne; Gebhardt, Anna J; Dieckow, Lynn; Riecken, Kristoffer; Fehse, Boris; Bannas, Peter; Magnus, Tim; Verdoes, Martijn; Figdor, Carl G; Hartlepp, Klaus F; Schleer, Hubertus; Füner, Jonas; Tomas, Nicola M; Haag, Friedrich; Rissiek, Björn; Mann, Anna M; Menzel, Stephan; Koch-Nolte, Friedrich.

in: NAT COMMUN, Jahrgang 15, Nr. 1, 03.06.2024, S. 4728.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Eden, T, Schaffrath, AZ, Wesolowski, J, Stähler, T, Tode, N, Richter, N, Schäfer, W, Hambach, J, Hermans-Borgmeyer, I, Woens, J, Le Gall, CM, Wendler, S, Linke-Winnebeck, C, Stobbe, M, Budnicki, I, Wanney, A, Heitz, Y, Schimmelpfennig, L, Schweitzer, L, Zimmer, D, Stahl, E, Seyfried, F, Gebhardt, AJ, Dieckow, L, Riecken, K, Fehse, B, Bannas, P, Magnus, T, Verdoes, M, Figdor, CG, Hartlepp, KF, Schleer, H, Füner, J, Tomas, NM, Haag, F, Rissiek, B, Mann, AM, Menzel, S & Koch-Nolte, F 2024, 'Generation of nanobodies from transgenic 'LamaMice' lacking an endogenous immunoglobulin repertoire', NAT COMMUN, Jg. 15, Nr. 1, S. 4728. https://doi.org/10.1038/s41467-024-48735-x

APA

Eden, T., Schaffrath, A. Z., Wesolowski, J., Stähler, T., Tode, N., Richter, N., Schäfer, W., Hambach, J., Hermans-Borgmeyer, I., Woens, J., Le Gall, C. M., Wendler, S., Linke-Winnebeck, C., Stobbe, M., Budnicki, I., Wanney, A., Heitz, Y., Schimmelpfennig, L., Schweitzer, L., ... Koch-Nolte, F. (2024). Generation of nanobodies from transgenic 'LamaMice' lacking an endogenous immunoglobulin repertoire. NAT COMMUN, 15(1), 4728. https://doi.org/10.1038/s41467-024-48735-x

Vancouver

Eden T, Schaffrath AZ, Wesolowski J, Stähler T, Tode N, Richter N et al. Generation of nanobodies from transgenic 'LamaMice' lacking an endogenous immunoglobulin repertoire. NAT COMMUN. 2024 Jun 3;15(1):4728. https://doi.org/10.1038/s41467-024-48735-x

Bibtex

@article{978a0456e135470d9446c613d479ca58,
title = "Generation of nanobodies from transgenic 'LamaMice' lacking an endogenous immunoglobulin repertoire",
abstract = "Due to their exceptional solubility and stability, nanobodies have emerged as powerful building blocks for research tools and therapeutics. However, their generation in llamas is cumbersome and costly. Here, by inserting an engineered llama immunoglobulin heavy chain (IgH) locus into IgH-deficient mice, we generate a transgenic mouse line, which we refer to as 'LamaMouse'. We demonstrate that LamaMice solely express llama IgH molecules without association to Igκ or λ light chains. Immunization of LamaMice with AAV8, the receptor-binding domain of the SARS-CoV-2 spike protein, IgE, IgG2c, and CLEC9A enabled us to readily select respective target-specific nanobodies using classical hybridoma and phage display technologies, single B cell screening, and direct cloning of the nanobody-repertoire into a mammalian expression vector. Our work shows that the LamaMouse represents a flexible and broadly applicable platform for a facilitated selection of target-specific nanobodies.",
keywords = "Animals, Single-Domain Antibodies/genetics, Camelids, New World/immunology, Immunoglobulin Heavy Chains/genetics, Mice, Transgenic, Mice, Spike Glycoprotein, Coronavirus/immunology, Lectins, C-Type/metabolism, SARS-CoV-2/immunology, Immunoglobulin E/immunology, Humans, Dependovirus/genetics, Immunoglobulin G/immunology, COVID-19/immunology, B-Lymphocytes/immunology",
author = "Thomas Eden and Schaffrath, {Alessa Z} and Janusz Wesolowski and Tobias St{\"a}hler and Natalie Tode and Nathalie Richter and Waldemar Sch{\"a}fer and Julia Hambach and Irm Hermans-Borgmeyer and Jannis Woens and {Le Gall}, {Camille M} and Sabrina Wendler and Christian Linke-Winnebeck and Martina Stobbe and Iwona Budnicki and Amelie Wanney and Yannic Heitz and Lena Schimmelpfennig and Laura Schweitzer and Dennis Zimmer and Erik Stahl and Fabienne Seyfried and Gebhardt, {Anna J} and Lynn Dieckow and Kristoffer Riecken and Boris Fehse and Peter Bannas and Tim Magnus and Martijn Verdoes and Figdor, {Carl G} and Hartlepp, {Klaus F} and Hubertus Schleer and Jonas F{\"u}ner and Tomas, {Nicola M} and Friedrich Haag and Bj{\"o}rn Rissiek and Mann, {Anna M} and Stephan Menzel and Friedrich Koch-Nolte",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = jun,
day = "3",
doi = "10.1038/s41467-024-48735-x",
language = "English",
volume = "15",
pages = "4728",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Generation of nanobodies from transgenic 'LamaMice' lacking an endogenous immunoglobulin repertoire

AU - Eden, Thomas

AU - Schaffrath, Alessa Z

AU - Wesolowski, Janusz

AU - Stähler, Tobias

AU - Tode, Natalie

AU - Richter, Nathalie

AU - Schäfer, Waldemar

AU - Hambach, Julia

AU - Hermans-Borgmeyer, Irm

AU - Woens, Jannis

AU - Le Gall, Camille M

AU - Wendler, Sabrina

AU - Linke-Winnebeck, Christian

AU - Stobbe, Martina

AU - Budnicki, Iwona

AU - Wanney, Amelie

AU - Heitz, Yannic

AU - Schimmelpfennig, Lena

AU - Schweitzer, Laura

AU - Zimmer, Dennis

AU - Stahl, Erik

AU - Seyfried, Fabienne

AU - Gebhardt, Anna J

AU - Dieckow, Lynn

AU - Riecken, Kristoffer

AU - Fehse, Boris

AU - Bannas, Peter

AU - Magnus, Tim

AU - Verdoes, Martijn

AU - Figdor, Carl G

AU - Hartlepp, Klaus F

AU - Schleer, Hubertus

AU - Füner, Jonas

AU - Tomas, Nicola M

AU - Haag, Friedrich

AU - Rissiek, Björn

AU - Mann, Anna M

AU - Menzel, Stephan

AU - Koch-Nolte, Friedrich

N1 - © 2024. The Author(s).

PY - 2024/6/3

Y1 - 2024/6/3

N2 - Due to their exceptional solubility and stability, nanobodies have emerged as powerful building blocks for research tools and therapeutics. However, their generation in llamas is cumbersome and costly. Here, by inserting an engineered llama immunoglobulin heavy chain (IgH) locus into IgH-deficient mice, we generate a transgenic mouse line, which we refer to as 'LamaMouse'. We demonstrate that LamaMice solely express llama IgH molecules without association to Igκ or λ light chains. Immunization of LamaMice with AAV8, the receptor-binding domain of the SARS-CoV-2 spike protein, IgE, IgG2c, and CLEC9A enabled us to readily select respective target-specific nanobodies using classical hybridoma and phage display technologies, single B cell screening, and direct cloning of the nanobody-repertoire into a mammalian expression vector. Our work shows that the LamaMouse represents a flexible and broadly applicable platform for a facilitated selection of target-specific nanobodies.

AB - Due to their exceptional solubility and stability, nanobodies have emerged as powerful building blocks for research tools and therapeutics. However, their generation in llamas is cumbersome and costly. Here, by inserting an engineered llama immunoglobulin heavy chain (IgH) locus into IgH-deficient mice, we generate a transgenic mouse line, which we refer to as 'LamaMouse'. We demonstrate that LamaMice solely express llama IgH molecules without association to Igκ or λ light chains. Immunization of LamaMice with AAV8, the receptor-binding domain of the SARS-CoV-2 spike protein, IgE, IgG2c, and CLEC9A enabled us to readily select respective target-specific nanobodies using classical hybridoma and phage display technologies, single B cell screening, and direct cloning of the nanobody-repertoire into a mammalian expression vector. Our work shows that the LamaMouse represents a flexible and broadly applicable platform for a facilitated selection of target-specific nanobodies.

KW - Animals

KW - Single-Domain Antibodies/genetics

KW - Camelids, New World/immunology

KW - Immunoglobulin Heavy Chains/genetics

KW - Mice, Transgenic

KW - Mice

KW - Spike Glycoprotein, Coronavirus/immunology

KW - Lectins, C-Type/metabolism

KW - SARS-CoV-2/immunology

KW - Immunoglobulin E/immunology

KW - Humans

KW - Dependovirus/genetics

KW - Immunoglobulin G/immunology

KW - COVID-19/immunology

KW - B-Lymphocytes/immunology

U2 - 10.1038/s41467-024-48735-x

DO - 10.1038/s41467-024-48735-x

M3 - SCORING: Journal article

C2 - 38830864

VL - 15

SP - 4728

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -