Generation of nanobodies from transgenic 'LamaMice' lacking an endogenous immunoglobulin repertoire.
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
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 Jun 2024
03 Jun 2024
Historique:
received:
23
10
2023
accepted:
02
05
2024
medline:
4
6
2024
pubmed:
4
6
2024
entrez:
3
6
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38830864
doi: 10.1038/s41467-024-48735-x
pii: 10.1038/s41467-024-48735-x
doi:
Substances chimiques
Single-Domain Antibodies
0
Immunoglobulin Heavy Chains
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Lectins, C-Type
0
Immunoglobulin E
37341-29-0
Immunoglobulin G
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4728Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB1328
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : No310/16
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB1192
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : COMMUTE
Informations de copyright
© 2024. The Author(s).
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