{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:43:02Z","timestamp":1771472582849,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:00:00Z","timestamp":1552953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI22040"],"award-info":[{"award-number":["AI22040"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA008748"],"award-info":[{"award-number":["CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary angioedema (<jats:styled-content style=\"fixed-case\">HAE<\/jats:styled-content>) is a life\u2010threatening, autosomal dominant disorder characterized by unpredictable, episodic swelling of the face, upper airway, oropharynx, extremities, genitalia, and gastrointestinal tract. Almost all cases of <jats:styled-content style=\"fixed-case\">HAE<\/jats:styled-content> are caused by mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">SERPING<\/jats:styled-content>1<\/jats:italic> gene resulting in a deficiency in functional plasma C1 esterase inhibitor (C1<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content>), a serine protease inhibitor that normally inhibits proteases in the contact, complement, and fibrinolytic systems. Current treatment of <jats:styled-content style=\"fixed-case\">HAE<\/jats:styled-content> includes long\u2010term prophylaxis with attenuated androgens or human plasma\u2010derived C1<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content> and management of acute attacks with human plasma\u2010derived or recombinant C1<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content>, bradykinin, and kallikrein inhibitors, each of which requires repeated administration. As an approach to effectively treat <jats:styled-content style=\"fixed-case\">HAE<\/jats:styled-content> with a single treatment, we hypothesized that a one\u2010time intravenous administration of an adeno\u2010associated virus (<jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>) gene transfer vector expressing the genetic sequence of the normal human C1 esterase inhibitor (<jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>rh.10hC1<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content>) would provide sustained circulating C1<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content> levels sufficient to prevent angioedema episodes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To study the efficacy of <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>rh.10hC1<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content>, we used <jats:styled-content style=\"fixed-case\">CRISPR<\/jats:styled-content>\/Cas9 technology to create a heterozygote C1<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content>\u2010deficient mouse model (S63\u00b1) that shares characteristics associated with <jats:styled-content style=\"fixed-case\">HAE<\/jats:styled-content> in humans including decreased plasma C1<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content> and C4 levels. Phenotypically, these mice have increased vascular permeability of skin and internal organs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Systemic administration of <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>rh.10hC1<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content> to the S63\u00b1 mice resulted in sustained human C1<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content> activity levels above the predicted therapeutic levels and correction of the vascular leak in skin and internal organs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A single treatment with <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>rh.10hC1<jats:styled-content style=\"fixed-case\">EI<\/jats:styled-content> has the potential to provide long\u2010term protection from angioedema attacks in affected individuals.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13582","type":"journal-article","created":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T15:50:11Z","timestamp":1532965811000},"page":"1081-1089","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Gene therapy for C1 esterase inhibitor deficiency in a Murine Model of Hereditary angioedema"],"prefix":"10.1111","volume":"74","author":[{"given":"Ting","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College New York New\u00a0York"},{"name":"Department of Respiratory Medicine KunShan Hospital of Traditional Chinese Medicine Kunshan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria J.","family":"Chiuchiolo","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College New York New\u00a0York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adele S.","family":"Whaley","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College New York New\u00a0York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony R.","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College New York New\u00a0York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolan","family":"Sondhi","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College New York New\u00a0York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen M.","family":"Kaminsky","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College New York New\u00a0York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald G.","family":"Crystal","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College New York New\u00a0York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Odelya E.","family":"Pagovich","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Weill Cornell Medical College New York New\u00a0York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.06.047"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp0803977"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.03.034"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1939-4551-4-S2-S9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.163.10.1229"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.12.114"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2013.08.019"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2015.36.3824"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.00492.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-14-71"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2013.05.028"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2008.12.001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.78.082107.133320"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.5-3-249"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-005-0001-4"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1078\/0171-2985-00153"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2013.12.023"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-016-8561-8"},{"key":"e_1_2_8_20_1","first-page":"S25","article-title":"The pathophysiology of hereditary angioedema","volume":"3","author":"Zuraw BL","year":"2010","journal-title":"World Allergy Organ J"},{"key":"e_1_2_8_21_1","unstructured":"C1 inhibiTor gene muTATion dATAbAse.2018.http:\/\/hae.enzim.hu\/. Accessed April 19 2018."},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2013.07.002"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14059"},{"key":"e_1_2_8_24_1","unstructured":"Berinert. [package insert]. Kankakee IL CSL Behring LLC.2009.http:\/\/labeling.cslbehring.com\/PI\/US\/Berinert\/EN\/Berinert-Prescribing-Information.pdf. Accessed January 12 2017."},{"key":"e_1_2_8_25_1","unstructured":"European Medicines Agency.Firazyr: Annex I: Summary of Product\u00a0Characteristics.2017.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/000899\/WC500022966.pdf. Accessed January 12 2017."},{"key":"e_1_2_8_26_1","unstructured":"Kalbitor. [package insert].Cambridge MA:Dyax Corp.2009.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/125277s071lbl.pdf. Accessed January 12 2017."},{"key":"e_1_2_8_27_1","unstructured":"Ruconest. [package insert].https:\/\/81b77e9a9bc9711e90b1-f416dd7f832b6e1ad8c969a90667ca99.ssl.cf1.rackcdn.com\/shared\/pi\/ruconest-pi.pdf. 2015. Accessed January 12 2017."},{"key":"e_1_2_8_28_1","unstructured":"CINRYZE. [package insert].Exton PA:ViroPharma Biologics Inc.2010.https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/BloodBloodProducts\/ApprovedProducts\/LicensedProductsBLAs\/FractionatedPlasmaProducts\/UCM129918.pdf. Accessed January 12 2017."},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613627"},{"key":"e_1_2_8_30_1","unstructured":"CSL Behring.HAEGARDA C1 esterase inhibitor subcutaneous (human).2017.https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/BloodBloodProducts\/ApprovedProducts\/LicensedProductsBLAs\/FractionatedPlasmaProducts\/UCM564335.pdf. Accessed January 12 2017."},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2013.34.3623"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)60506-6"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.2500\/ar.2017.8.0192"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2017.05.017"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2010.01.024"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2015.01.003"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2016.03.024"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148362"},{"key":"e_1_2_8_39_1","volume-title":"Manipulating the Mouse Embryo: A Laboratory Manual","author":"Hogan B","year":"1994"},{"key":"e_1_2_8_40_1","first-page":"324","article-title":"Long\u2010term expression and safety of administration of AAVrh. 10hCLN2 to the brain of rats and nonhuman primates for the treatment of late infantile neuronal ceroid lipofuscinosis. Hum Gene Ther","volume":"23","author":"Sondhi D","year":"2012","journal-title":"Methods"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2005.09.003"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200214211"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5449.2511"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-09-2889"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2006.03.014"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.119"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.161.20.2417"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-9-44"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/WOX.0b013e318279affa"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2016.1104300"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.07.017"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(03)00130-5"},{"key":"e_1_2_8_53_1","unstructured":"NCBI.HomoloGene:44. Gene conserved in Euteleostomi. National Library of Medicine.https:\/\/www.ncbi.nlm.nih.gov\/homologene\/44. Accessed May 6 2018."},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.274"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302549"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1089\/humc.2013.168"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fall.13582","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.13582","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/all.13582","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.13582","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T08:38:14Z","timestamp":1694335094000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.13582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,19]]},"references-count":55,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1111\/all.13582"],"URL":"https:\/\/doi.org\/10.1111\/all.13582","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,19]]},"assertion":[{"value":"2018-04-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}