ArticleProceedings of the National Academy of Sciences of the United States of America2010
Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 146 citations in OpenAlex.
- Viral Vector Based Immunotherapy for Peanut Allergy.Viruses · 2024Review
- Factor IX administration in the skin primes inhibitor formation and sensitizes hemophilia B mice to systemic factor IX administration.Research and practice in thrombosis and haemostasis · 2023Article
- Review
- Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice.Cellular immunology · 2023Article
- Plant-made pharmaceuticals: exploring studies for the production of recombinant protein in plants and assessing challenges ahead.Plant biotechnology reports · 2023Review
- Distinct functions and transcriptional signatures in orally induced regulatory T cell populations.Frontiers in immunology · 2023Article
- Oral tolerance to prevent anti-drug antibody formation in protein replacement therapies.Cellular immunology · 2022Review
- The production of the first functional antibody mimetic in higher plants: the chloroplast makes the DARPin G3 for HER2 imaging in oncology.Biological research · 2022Article
- Seed- and leaf-based expression of FGF21-transferrin fusion proteins for oral delivery and treatment of non-alcoholic steatohepatitis.Frontiers in plant science · 2022Article
- Preclinical development of plant-based oral immune modulatory therapy for haemophilia B.Plant biotechnology journal · 2021Article
- Oral delivery of therapeutic proteins bioencapsulated in plant cells: preclinical and clinical advances.Current opinion in colloid & interface science · 2021Article
- Role of orally induced regulatory T cells in immunotherapy and tolerance.Cellular immunology · 2021Review
- Plant-Produced Vaccines: Future Applications in Aquaculture.Frontiers in plant science · 2021Review
- Plastid Transformation: How Does it Work? Can it Be Applied to Crops? What Can it Offer?International journal of molecular sciences · 2020Review
- Investigational new drug enabling angiotensin oral-delivery studies to attenuate pulmonary hypertension.Biomaterials · 2020Article
- Role of Small Intestine and Gut Microbiome in Plant-Based Oral Tolerance for Hemophilia.Frontiers in immunology · 2020Article
- Plant cell-made protein antigens for induction of Oral tolerance.Biotechnology advances · 2019Review
- Cold chain and virus-free oral polio booster vaccine made in lettuce chloroplasts confers protection against all three poliovirus serotypes.Plant biotechnology journal · 2019Article
- Evaluation of lettuce chloroplast and soybean cotyledon as platforms for production of functional bone morphogenetic protein 2.Transgenic research · 2019Article
- Critical Evaluation of Strategies for the Production of Blood Coagulation Factors in Plant-Based Systems.Frontiers in plant science · 2019Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia or other inherited protein deficiencies, we have developed a prophylactic protocol using a murine hemophilia B model. Oral delivery of coagulation factor IX fused with cholera toxin beta-subunit (with or without a furin cleavage site; CTB-FFIX or CTB-FIX), expressed in chloroplasts (up to 3.8% soluble protein or 0.4 mg/g leaf tissue), bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies (undetectable or up to 100-fold less than controls). Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous F.IX. Whereas only 20-25% of control animals survived after six to eight F.IX doses, 90-93% of F.IX-fed mice survived 12 injections without signs of allergy or anaphylaxis. Immunostaining confirmed delivery of F.IX to Peyer's patches in the ileum. Within 2-5 h, feeding of CTB-FFIX additionally resulted in systemic delivery of F.IX antigen. This high-responder strain of hemophilia B mice represents a new animal model to study anaphylactic reactions. The protocol was effective over a range of oral antigen doses (equivalent to 5-80 microg recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (approximately 40% life span of this mouse strain). Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost-effective and efficient approach of antigen delivery to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment.
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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.