ArticleAllergy2019
Gene therapy for C1 esterase inhibitor deficiency in a Murine Model of Hereditary angioedema.
Article in Allergy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 46 citations in OpenAlex.
- Friend or foe: assessing the value of animal models for facilitating clinical breakthroughs in complement research.The Journal of clinical investigation · 2025Review
- Hereditary Angioedema and Venous Thromboembolism: Where There's Smoke, There's Fire.Seminars in thrombosis and hemostasis · 2025Review
- The double whammy of ER-retention and dominant-negative effects in numerous autosomal dominant diseases: significance in disease mechanisms and therapy.Journal of biomedical science · 2024Review
- Gene Therapy for Immunoglobulin E, Complement-Mediated, and Eosinophilic Disorders.Human gene therapy · 2023Review
- C1 inhibitor deficiency enhances contact pathway-mediated activation of coagulation and venous thrombosis.Blood · 2023Article
- A novel murine in vivo model for acute hereditary angioedema attacks.Scientific reports · 2021Article
- Current and Prospective Targets of Pharmacologic Treatment of Hereditary Angioedema Types 1 and 2.Clinical reviews in allergy & immunology · 2021Review
- Safety of Direct Intraparenchymal AAVrh.10-Mediated Central Nervous System Gene Therapy for Metachromatic Leukodystrophy.Human gene therapy · 2021Article
- Leveraging Genetics for Hereditary Angioedema: A Road Map to Precision Medicine.Clinical reviews in allergy & immunology · 2021Review
- Clinical manifestations of hereditary angioedema and a systematic review of treatment options.Laryngoscope investigative otolaryngology · 2021Review
- Deep Intronic SERPING1 Gene Variants: Ending One Odyssey and Starting Another?Journal of clinical immunology · 2021Article
- European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management.Journal of clinical immunology · 2020Article
- [Hereditary angioedema].Der Internist · 2019Review
- Advances in drug allergy, urticaria, angioedema, and anaphylaxis in 2018.The Journal of allergy and clinical immunology · 2019Review
- Lanadelumab for the Prophylactic Treatment of Hereditary Angioedema with C1 Inhibitor Deficiency: A Review of Preclinical and Phase I Studies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2019Review
- Dominant-negative SERPING1 variants cause intracellular retention of C1 inhibitor in hereditary angioedema.The Journal of clinical investigation · 2019Article
- Lanadelumab Injection Treatment For The Prevention Of Hereditary Angioedema (HAE): Design, Development And Place In Therapy.Drug design, development and therapy · 2019Review
- Breakthroughs in hereditary angioedema management: a systematic review of approved drugs and those under research.Drugs in context · 2019Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundHereditary angioedema (HAE) is a life-threatening, autosomal dominant disorder characterized by unpredictable, episodic swelling of the face, upper airway, oropharynx, extremities, genitalia, and gastrointestinal tract. Almost all cases of HAE are caused by mutations in the SERPING1 gene resulting in a deficiency in functional plasma C1 esterase inhibitor (C1EI), a serine protease inhibitor that normally inhibits proteases in the contact, complement, and fibrinolytic systems. Current treatment of HAE includes long-term prophylaxis with attenuated androgens or human plasma-derived C1EI and management of acute attacks with human plasma-derived or recombinant C1EI, bradykinin, and kallikrein inhibitors, each of which requires repeated administration. As an approach to effectively treat HAE with a single treatment, we hypothesized that a one-time intravenous administration of an adeno-associated virus (AAV) gene transfer vector expressing the genetic sequence of the normal human C1 esterase inhibitor (AAVrh.10hC1EI) would provide sustained circulating C1EI levels sufficient to prevent angioedema episodes.
methodsTo study the efficacy of AAVrh.10hC1EI, we used CRISPR/Cas9 technology to create a heterozygote C1EI-deficient mouse model (S63±) that shares characteristics associated with HAE in humans including decreased plasma C1EI and C4 levels. Phenotypically, these mice have increased vascular permeability of skin and internal organs.
resultsSystemic administration of AAVrh.10hC1EI to the S63± mice resulted in sustained human C1EI activity levels above the predicted therapeutic levels and correction of the vascular leak in skin and internal organs.
conclusionA single treatment with AAVrh.10hC1EI has the potential to provide long-term protection from angioedema attacks in affected individuals.
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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.