ArticleProceedings of the National Academy of Sciences of the United States of America2014
Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
212 citing papers in PubMed, 3 syntheses or guidelines pooled it, 378 citations in OpenAlex.
- Effectiveness and safety of systemic therapy for moderate-to-severe atopic dermatitis in children and adolescent patients: a systematic review.Frontiers in immunology · 2024Pooled it
- Biotechnology Approaches for the Treatment of Dyslipidemia.Cardiovascular drugs and therapy · 2021Pooled it
- Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS).The British journal of dermatology · 2020Pooled it
- Pharmacokinetics, Immunogenicity, and Safety of a Modified YTE Antibody in Healthy Adults.Clinical pharmacology in drug development · 2026Trial
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- Dupilumab in Patients With Chronic Spontaneous Urticaria: Phase 3 LIBERTY-CSU CUPID Randomized Clinical Trials.JAMA dermatology · 2026Trial
- Dupilumab Treatment Up to 5 Years Shows No Clinically Meaningful Changes in Laboratory Parameters in Adults with Moderate-to-Severe Atopic Dermatitis.Advances in therapy · 2026Trial
- Dupilumab Efficacy in Children With Eosinophilic Esophagitis With Prior Swallowed Topical Corticosteroid Use: A Subgroup Analysis.The American journal of gastroenterology · 2026Trial
- Peak Nasal Inspiratory Flow and the Association with Nasal Obstruction in Patients with Severe CRSwNP from the SINUS-24/-52 Studies.Advances in therapy · 2025Trial
- Dupilumab efficacy by disease severity in pediatric type 2 asthma.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2025Trial
- Dupilumab Efficacy and Safety in Patients With Persistent Asthma: Asia-Pacific Region.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2025Trial
- Dupilumab Plus Medium-Dose Inhaled Corticosteroid (ICS) Improves Outcomes Compared With Placebo Plus Continued High-Dose ICS in Children With Uncontrolled Moderate-to-Severe Type 2 Asthma.Pediatric pulmonology · 2025Trial
- A TMPRSS6-inhibiting mAb improves disease in a β-thalassemia mouse model and reduces iron in healthy humans.JCI insight · 2025Trial
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- GDF8 and activin A are the key negative regulators of muscle mass in postmenopausal females: a randomized phase I trial.Nature communications · 2025Trial
- Dupilumab as an Adjunct to Oral Immunotherapy in Pediatric Patients With Peanut Allergy.Allergy · 2025Trial
- Association Between Smell Loss, Disease Burden, and Dupilumab Efficacy in Chronic Rhinosinusitis with Nasal Polyps.American journal of rhinology & allergy · 2025Trial
- Dupilumab is Efficacious in Young Children with Atopic Dermatitis Regardless of Type 2 Comorbidities.Advances in therapy · 2024Trial
- Cemiplimab monotherapy in Japanese patients with recurrent or metastatic cervical cancer.Cancer medicine · 2024Trial
152 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Genetic humanization, which involves replacing mouse genes with their human counterparts, can create powerful animal models for the study of human genes and diseases. One important example of genetic humanization involves mice humanized for their Ig genes, allowing for human antibody responses within a mouse background (HumAb mice) and also providing a valuable platform for the generation of fully human antibodies as therapeutics. However, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which they were genetically humanized. Heretofore, most genetic humanizations have involved disruption of the endogenous mouse gene with simultaneous introduction of a human transgene at a new and random location (so-called KO-plus-transgenic humanization). More recent efforts have attempted to replace mouse genes with their human counterparts at the same genetic location (in situ humanization), but such efforts involved laborious procedures and were limited in size and precision. We describe a general and efficient method for very large, in situ, and precise genetic humanization using large compound bacterial artificial chromosome-based targeting vectors introduced into mouse ES cells. We applied this method to genetically humanize 3-Mb segments of both the mouse heavy and κ light chain Ig loci, by far the largest genetic humanizations ever described. This paper provides a detailed description of our genetic humanization approach, and the companion paper reports that the humoral immune systems of mice bearing these genetically humanized loci function as efficiently as those of WT mice.
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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.