ArticleNature communications2019
An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 62 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- FcRn as a Transporter for Nasal Delivery of Biologics: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Article
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- Engineering Protein-Based HIV Entry Inhibitors: Advances, Challenges, and Translational Strategies.Biomolecules · 2026Review
- Lymph node fine-tuning FcγR signaling boosts anti-PD-1 therapy.Journal for immunotherapy of cancer · 2026Article
- Lymph node microenvironment remodeling unlocks local antibody-mediated B cell depletion.Science advances · 2026Article
- A functional investigation of antibody Fc-FcRn variant binding guided bybioRxiv : the preprint server for biology · 2026Article
- Comparative assessment of tissue cross-reactivity and pharmacokinetic half-life of malaria monoclonal antibodies.Frontiers in immunology · 2026Article
- The S190R mutation in RSV-A F protein impairs nirsevimab binding and neutralization capacity.Virus evolution · 2026Article
- Selective decoupling of IgG1 binding to viral Fc receptors restores antibody-mediated NK cell activation against HCMV.Cell reports · 2025Article
- Review
- A long-lasting prolactin stimulates galactopoiesis in mice.iScience · 2025Article
- Conserved heavy/light contacts and germline preferences revealed by a large-scale analysis of natively paired human antibody sequences and structural data.Communications biology · 2025Article
- Passive Immunization in the Prevention and Treatment of Viral Infections.European journal of immunology · 2025Review
- Engineering FcRn binding kinetics dramatically extends antibody serum half-life and enhances therapeutic potential.Journal of biological engineering · 2025Article
- Strategies for long-acting drug design.Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Review
- Optimising Monoclonal Antibody Drug Development for Inflammatory Bowel Disease.Clinical and experimental gastroenterology · 2025Review
- Engineered serum markers for non-invasive monitoring of gene expression in the brain.Nature biotechnology · 2024Article
- Respiratory Syncytial Virus and US Pediatric Intensive Care Utilization.JAMA network open · 2024Article
- Engineering of pH-dependent antigen binding properties for toxin-targeting IgG1 antibodies using light-chain shuffling.Structure (London, England : 1993) · 2024Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 9 institutions in 3 countries.
Funding
Abstract
The pharmacokinetic properties of antibodies are largely dictated by the pH-dependent binding of the IgG fragment crystallizable (Fc) domain to the human neonatal Fc receptor (hFcRn). Engineered Fc domains that confer a longer circulation half-life by virtue of more favorable pH-dependent binding to hFcRn are of great therapeutic interest. Here we developed a pH Toggle switch Fc variant containing the L309D/Q311H/N434S (DHS) substitutions, which exhibits markedly improved pharmacokinetics relative to both native IgG1 and widely used half-life extension variants, both in conventional hFcRn transgenic mice and in new knock-in mouse strains. engineered specifically to recapitulate all the key processes relevant to human antibody persistence in circulation, namely: (i) physiological expression of hFcRn, (ii) the impact of hFcγRs on antibody clearance and (iii) the role of competing endogenous IgG. DHS-IgG retains intact effector functions, which are important for the clearance of target pathogenic cells and also has favorable developability.
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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.