{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:18:20Z","timestamp":1781104700472,"version":"3.54.1"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,4,13]]},"abstract":"<jats:p>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 \u03b2-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\u201325% of control animals survived after six to eight F.IX doses, 90\u201393% 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\u20135 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\u201380 \u03bcg recombinant F.IX\/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (\u223c40% 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.<\/jats:p>","DOI":"10.1073\/pnas.0912181107","type":"journal-article","created":{"date-parts":[[2010,3,29]],"date-time":"2010-03-29T23:49:26Z","timestamp":1269906566000},"page":"7101-7106","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":123,"title":["Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice"],"prefix":"10.1073","volume":"107","author":[{"given":"Dheeraj","family":"Verma","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, College of Medicine, University of Central Florida, Orlando, FL 32816-2364; 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