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, Vol. 15, No. 1, 03.06.2024, p. 4728.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -