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Generation of nanobodies from transgenic ‘LamaMice’ lacking an endogenous immunoglobulin repertoire

Author

Listed:
  • Thomas Eden

    (University Medical Center Hamburg-Eppendorf)

  • Alessa Z. Schaffrath

    (University Medical Center Hamburg-Eppendorf)

  • Janusz Wesolowski

    (University Medical Center Hamburg-Eppendorf)

  • Tobias Stähler

    (University Medical Center Hamburg-Eppendorf)

  • Natalie Tode

    (University Medical Center Hamburg-Eppendorf)

  • Nathalie Richter

    (University Medical Center Hamburg-Eppendorf)

  • Waldemar Schäfer

    (University Medical Center Hamburg-Eppendorf)

  • Julia Hambach

    (University Medical Center Hamburg-Eppendorf)

  • Irm Hermans-Borgmeyer

    (University Medical Center Hamburg-Eppendorf)

  • Jannis Woens

    (University Medical Center Hamburg-Eppendorf)

  • Camille M. Gall

    (Radboud University Medical Center)

  • Sabrina Wendler

    (Germany - A part of Proteintech Group)

  • Christian Linke-Winnebeck

    (Germany - A part of Proteintech Group)

  • Martina Stobbe

    (Germany - A part of Proteintech Group)

  • Iwona Budnicki

    (Genovac GmbH)

  • Amelie Wanney

    (Genovac GmbH)

  • Yannic Heitz

    (Genovac GmbH)

  • Lena Schimmelpfennig

    (Genovac GmbH)

  • Laura Schweitzer

    (Genovac GmbH)

  • Dennis Zimmer

    (Genovac GmbH)

  • Erik Stahl

    (Preclinics GmbH)

  • Fabienne Seyfried

    (University Medical Center Hamburg-Eppendorf)

  • Anna J. Gebhardt

    (University Medical Center Hamburg-Eppendorf)

  • Lynn Dieckow

    (University Medical Center Hamburg-Eppendorf)

  • Kristoffer Riecken

    (University Medical Center Hamburg-Eppendorf)

  • Boris Fehse

    (University Medical Center Hamburg-Eppendorf)

  • Peter Bannas

    (University Medical Center Hamburg-Eppendorf)

  • Tim Magnus

    (University Medical Center Hamburg-Eppendorf)

  • Martijn Verdoes

    (Radboud University Medical Center)

  • Carl G. Figdor

    (Radboud University Medical Center)

  • Klaus F. Hartlepp

    (Germany - A part of Proteintech Group)

  • Hubertus Schleer

    (Genovac GmbH)

  • Jonas Füner

    (Preclinics GmbH)

  • Nicola M. Tomas

    (University Medical Center Hamburg-Eppendorf)

  • Friedrich Haag

    (University Medical Center Hamburg-Eppendorf)

  • Björn Rissiek

    (University Medical Center Hamburg-Eppendorf)

  • Anna M. Mann

    (University Medical Center Hamburg-Eppendorf)

  • Stephan Menzel

    (University Medical Center Hamburg-Eppendorf
    University of Bonn)

  • Friedrich Koch-Nolte

    (University Medical Center Hamburg-Eppendorf)

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.

Suggested Citation

  • Thomas Eden & Alessa Z. Schaffrath & Janusz Wesolowski & Tobias Stähler & Natalie Tode & Nathalie Richter & Waldemar Schäfer & Julia Hambach & Irm Hermans-Borgmeyer & Jannis Woens & Camille M. Gall & , 2024. "Generation of nanobodies from transgenic ‘LamaMice’ lacking an endogenous immunoglobulin repertoire," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48735-x
    DOI: 10.1038/s41467-024-48735-x
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    References listed on IDEAS

    as
    1. Leo Hanke & Hrishikesh Das & Daniel J. Sheward & Laura Perez Vidakovics & Egon Urgard & Ainhoa Moliner-Morro & Changil Kim & Vivien Karl & Alec Pankow & Natalie L. Smith & Bartlomiej Porebski & Oscar , 2022. "A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
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