ArticleNature biotechnology2014
Complete humanization of the mouse immunoglobulin loci enables efficient therapeutic antibody discovery.
Article in Nature biotechnology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
113 citing papers in PubMed, 184 citations in OpenAlex.
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- CRISPR-mediated precise large fragment insertion in zygotes enables rapid generation of humanized immunoglobulin heavy-chain mice.Immunity · 2026Article
- Establishing human immune system mice: application, opportunity, and challenges.Experimental & molecular medicine · 2026Review
- Recurrent SARS-CoV-2 Omicron broadly neutralizing humanized antibodies in different single human VProceedings of the National Academy of Sciences of the United States of America · 2026Article
- A scalable two-step genome editing strategy for generating full-length gene-humanized mice at diverse genomic loci.Nature communications · 2026Article
- Synthetic rewriting technologies in mammalian cells.Nature communications · 2026Review
- Laboratory-Scale Production of Recombinant IgG Antibodies.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Leveraging single B cell antibody platforms to develop countermeasures against animal viral diseases: recent advances and future perspectives.Frontiers in veterinary science · 2026Review
- Technological advancements in antibody-based therapeutics for treatment of diseases.Journal of biomedical science · 2025Review
- HuAbDiffusion: a discrete language diffusion model used for antibody humanization.Briefings in bioinformatics · 2025Article
- Preclinical ex vivo and in vivo models to study immunotherapy agents and their combinations as predictive tools toward the clinic.Journal for immunotherapy of cancer · 2025Review
- citrOgen: a synthesis-free polysaccharide and protein antigen-presentation to antibody-induction platform.Nature communications · 2025Article
- Human Genome REWRITE for Off-the-Shelf Stem Cells Reveals an "Epigenetic Ghost".bioRxiv : the preprint server for biology · 2025Article
- Fifty years of monoclonals: the past, present and future of antibody therapeutics.Nature reviews. Immunology · 2025Article
- Integrative and Emerging Models in Antibody Research: A Comprehensive Review.Antibody therapeutics · 2025Review
- Development and in vitro characterization of humanized antibodies for blocking human TRPM4 channel.Scientific reports · 2025Article
- Targeting Bottlenecks in Malaria Transmission: Antibody-Epitope Descriptions Guide the Design of Next-Generation Biomedical Interventions.Immunological reviews · 2025Review
- A Transgenic Mouse With a Humanized B-Cell Repertoire Mounts an Antibody Response to Influenza Infection and Vaccination.The Journal of infectious diseases · 2025Article
- Solubilization of Membrane Proteins using designed protein WRAPS.bioRxiv : the preprint server for biology · 2025Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
37 authors at 2 institutions in 1 country.
Funding
Abstract
If immunized with an antigen of interest, transgenic mice with large portions of unrearranged human immunoglobulin loci can produce fully human antigen-specific antibodies; several such antibodies are in clinical use. However, technical limitations inherent to conventional transgenic technology and sequence divergence between the human and mouse immunoglobulin constant regions limit the utility of these mice. Here, using repetitive cycles of genome engineering in embryonic stem cells, we have inserted the entire human immunoglobulin variable-gene repertoire (2.7 Mb) into the mouse genome, leaving the mouse constant regions intact. These transgenic mice are viable and fertile, with an immune system resembling that of wild-type mice. Antigen immunization results in production of high-affinity antibodies with long human-like complementarity-determining region 3 (CDR3H), broad epitope coverage and strong signatures of somatic hypermutation. These mice provide a robust system for the discovery of therapeutic human monoclonal antibodies; as a surrogate readout of the human antibody response, they may also aid vaccine design efforts.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.