{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:53:35Z","timestamp":1791597215320,"version":"4.3.4"},"reference-count":44,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"am","delay-in-days":367,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270026"],"award-info":[{"award-number":["82270026"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070939"],"award-info":[{"award-number":["32070939"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030106"],"award-info":[{"award-number":["82030106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jacionline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Allergy and Clinical Immunology"],"published-print":{"date-parts":[[2024,10]]},"DOI":"10.1016\/j.jaci.2024.05.027","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T13:12:50Z","timestamp":1718111570000},"page":"1008-1021","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":25,"title":["A novel inhalable nanobody targeting IL-4R\u03b1 for the treatment of asthma"],"prefix":"10.1016","volume":"154","author":[{"given":"Min","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyu","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Gai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaiyu","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baihe","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakun","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jaci.2024.05.027_bib1","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S0169-409X(03)00077-2","article-title":"Inhalation therapy: technological milestones in asthma treatment","volume":"55","author":"Dalby","year":"2003","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1016\/j.jaci.2024.05.027_bib2","doi-asserted-by":"crossref","DOI":"10.1016\/j.rmed.2022.106949","article-title":"The impact of inhaler technique on clinical outcomes in adolescents and adults with asthma: a systematic review","volume":"202","author":"Roche","year":"2022","journal-title":"Respir Med"},{"key":"10.1016\/j.jaci.2024.05.027_bib3","first-page":"131","article-title":"Inhalation drug delivery devices: technology update","volume":"8","author":"Ibrahim","year":"2015","journal-title":"Med Devices (Auckl)"},{"key":"10.1016\/j.jaci.2024.05.027_bib4","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1056\/NEJMra2032506","article-title":"Biologic therapies for severe asthma","volume":"386","author":"Brusselle","year":"2022","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2024.05.027_bib5","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1164\/rccm.201810-1944CI","article-title":"Role of biologics in asthma","volume":"199","author":"McGregor","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2024.05.027_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2020.114012","article-title":"Promises and challenges of biologics for severe asthma","volume":"179","author":"Tan","year":"2020","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.jaci.2024.05.027_bib7","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1111\/imj.15904","article-title":"Overview of recent advancements in asthma management","volume":"52","author":"Witt","year":"2022","journal-title":"Intern Med J"},{"key":"10.1016\/j.jaci.2024.05.027_bib8","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1517\/14712590802496928","article-title":"Biologics in asthma: difficulties and drawbacks","volume":"8","author":"Bousquet","year":"2008","journal-title":"Expert Opin Biol Ther"},{"key":"10.1016\/j.jaci.2024.05.027_bib9","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/rr40","article-title":"Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists","volume":"2","author":"Steinke","year":"2001","journal-title":"Respir Res"},{"key":"10.1016\/j.jaci.2024.05.027_bib10","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1097\/MCP.0000000000000436","article-title":"Targeting the interleukin-4 and interleukin-13 pathways in severe asthma: current knowledge and future needs","volume":"24","author":"Parulekar","year":"2018","journal-title":"Curr Opin Pulm Med"},{"key":"10.1016\/j.jaci.2024.05.027_bib11","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.jaip.2019.11.020","article-title":"Diagnosis and management of T2-high asthma","volume":"8","author":"Coverstone","year":"2020","journal-title":"J Allergy Clin Immunol Pract"},{"key":"10.1016\/j.jaci.2024.05.027_bib12","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S0091-6749(98)70029-6","article-title":"Expression of the IL-4 receptor alpha-subunit is increased in bronchial biopsy specimens from atopic and nonatopic asthmatic subjects","volume":"102","author":"Kotsimbos","year":"1998","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2024.05.027_bib13","doi-asserted-by":"crossref","first-page":"23514","DOI":"10.1074\/jbc.M604292200","article-title":"Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn)","volume":"281","author":"Dall\u2019Acqua","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jaci.2024.05.027_bib14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrd.2018.183","article-title":"Non-invasive delivery strategies for biologics","volume":"18","author":"Anselmo","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.jaci.2024.05.027_bib15","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.xphs.2023.02.010","article-title":"Protein aggregates in inhaled biologics: challenges and considerations","volume":"112","author":"Ibrahim","year":"2023","journal-title":"J Pharm Sci"},{"key":"10.1016\/j.jaci.2024.05.027_bib16","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-animal-021419-083831","article-title":"Applications of nanobodies","volume":"9","author":"Muyldermans","year":"2021","journal-title":"Annu Rev Anim Biosci"},{"key":"10.1016\/j.jaci.2024.05.027_bib17","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.pharmthera.2016.06.012","article-title":"Nanobodies as inhaled biotherapeutics for lung diseases","volume":"169","author":"Van Heeke","year":"2017","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.jaci.2024.05.027_bib18","doi-asserted-by":"crossref","first-page":"7934","DOI":"10.1038\/s41598-018-26338-z","article-title":"The structural basis of nanobody unfolding reversibility and thermoresistance","volume":"8","author":"Kunz","year":"2018","journal-title":"Sci Rep"},{"key":"10.1016\/j.jaci.2024.05.027_bib19","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.pep.2018.11.001","article-title":"An efficient constitutive expression system for Anti-CEACAM5 nanobody production in the yeast Pichia pastoris","volume":"155","author":"Chen","year":"2019","journal-title":"Protein Expr Purif"},{"key":"10.1016\/j.jaci.2024.05.027_bib20","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ejpb.2021.04.003","article-title":"Oral inhalation for delivery of proteins and peptides to the lungs","volume":"163","author":"Frohlich","year":"2021","journal-title":"Eur J Pharm Biopharm"},{"key":"10.1016\/j.jaci.2024.05.027_bib21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/mco2.60","article-title":"A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential","volume":"2","author":"Gai","year":"2021","journal-title":"MedComm (2020)"},{"key":"10.1016\/j.jaci.2024.05.027_bib22","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1128\/AAC.01802-15","article-title":"Generation and characterization of ALX-0171, a potent novel therapeutic nanobody for the treatment of respiratory syncytial virus infection","volume":"60","author":"Detalle","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.jaci.2024.05.027_bib23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S2213-2600(20)30320-9","article-title":"Nebulised ALX-0171 for respiratory syncytial virus lower respiratory tract infection in hospitalised children: a double-blind, randomised, placebo-controlled, phase 2b trial","volume":"9","author":"Cunningham","year":"2021","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.jaci.2024.05.027_bib24","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jaci.2020.06.012","article-title":"Atopic dermatitis displays stable and dynamic skin transcriptome signatures","volume":"147","author":"M\u00f6bus","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2024.05.027_bib25","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.jaci.2014.10.013","article-title":"Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis","volume":"134","author":"Hamilton","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2024.05.027_bib26","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.851940","article-title":"Interleukins 4 and 13 in asthma: key pathophysiologic cytokines and druggable molecular targets","volume":"13","author":"Pelaia","year":"2022","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.jaci.2024.05.027_bib27","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.3389\/fphys.2019.01514","article-title":"Interleukin-5 in the pathophysiology of severe asthma","volume":"10","author":"Pelaia","year":"2019","journal-title":"Front Physiol"},{"key":"10.1016\/j.jaci.2024.05.027_bib28","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.jaci.2007.03.048","article-title":"Eosinophil trafficking in allergy and asthma","volume":"119","author":"Rosenberg","year":"2007","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2024.05.027_bib29","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.5415\/apallergy.2020.10.e14","article-title":"Mechanisms of eosinophilic inflammation","volume":"10","author":"Nagata","year":"2020","journal-title":"Asia Pacific Allergy"},{"key":"10.1016\/j.jaci.2024.05.027_bib30","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.jaci.2022.12.815","article-title":"Elarekibep (PRS-060\/AZD1402), a new class of inhaled Anticalin medicine targeting IL-4Ra for type 2 endotype asthma","volume":"151","author":"Matschiner","year":"2023","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2024.05.027_bib31","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1056\/NEJMoa1804092","article-title":"Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma","volume":"378","author":"Castro","year":"2018","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2024.05.027_bib44","series-title":"Pieris Pharmaceuticals Announces Successful Completion of Safety Milestone and Initiation of Efficacy Portion of Phase 2a Trial of PRS-060\/AZD1402","year":"2022"},{"key":"10.1016\/j.jaci.2024.05.027_bib33","series-title":"Drug delivery to the brain: physiological concepts, methodologies and approaches","first-page":"461","article-title":"Intranasal drug delivery to the brain","author":"Lochhead","year":"2022"},{"key":"10.1016\/j.jaci.2024.05.027_bib32","first-page":"A7476","article-title":"First-in-human data for the inhaled IL-4R\u03b1 antagonist AZD1402\/PRS-060 reveals a promising clinical profile for the treatment of asthma","volume":"199","author":"Bruns","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2024.05.027_bib34","series-title":"Pieris Pharmaceuticals announces AstraZeneca discontinuation of phase 2a trial of elarekibep (PRS-060\/AZD1402) due to new non-clinical safety findings from 13-week toxicology study","year":"2023"},{"key":"10.1016\/j.jaci.2024.05.027_bib35","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/S1542-0124(11)70022-2","article-title":"Tear lipocalin: structure and function","volume":"9","author":"Dartt","year":"2011","journal-title":"Ocul Surf"},{"key":"10.1016\/j.jaci.2024.05.027_bib36","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1167\/iovs.05-0176","article-title":"Interaction of purified tear lipocalin with lipid membranes","volume":"46","author":"Saaren-Seppala","year":"2005","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.jaci.2024.05.027_bib37","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1177\/002215540205000314","article-title":"Human lipocalin-1, a physiological scavenger of lipophilic compounds, is produced by corticotrophs of the pituitary gland","volume":"50","author":"Wojnar","year":"2002","journal-title":"J Histochem Cytochem"},{"key":"10.1016\/j.jaci.2024.05.027_bib38","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1016\/j.fertnstert.2011.01.141","article-title":"Lipocalin-1: a potential marker for noninvasive aneuploidy screening","volume":"95","author":"McReynolds","year":"2011","journal-title":"Fertil Steril"},{"key":"10.1016\/j.jaci.2024.05.027_bib39","doi-asserted-by":"crossref","first-page":"543","DOI":"10.2147\/COPD.S62700","article-title":"Increased serum levels of lipocalin-1 and -2 in patients with stable chronic obstructive pulmonary disease","volume":"9","author":"Wang","year":"2014","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"10.1016\/j.jaci.2024.05.027_bib40","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1007\/s40265-018-0989-0","article-title":"Caplacizumab: first global approval","volume":"78","author":"Duggan","year":"2018","journal-title":"Drugs"},{"key":"10.1016\/j.jaci.2024.05.027_bib41","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1080\/14712598.2023.2231344","article-title":"Ozoralizumab: first Nanobody therapeutic for rheumatoid arthritis","volume":"23","author":"Tanaka","year":"2023","journal-title":"Expert Opin Biol Ther"},{"key":"10.1016\/j.jaci.2024.05.027_bib42","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s40265-022-01671-w","article-title":"Envafolimab: first approval","volume":"82","author":"Markham","year":"2022","journal-title":"Drugs"},{"key":"10.1016\/j.jaci.2024.05.027_bib43","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/s41591-021-01622-0","article-title":"Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial","volume":"28","author":"Fowler","year":"2022","journal-title":"Nat Med"}],"container-title":["Journal of Allergy and Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674924005736?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674924005736?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T04:45:23Z","timestamp":1762231523000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0091674924005736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["S0091674924005736"],"URL":"https:\/\/doi.org\/10.1016\/j.jaci.2024.05.027","relation":{},"ISSN":["0091-6749"],"issn-type":[{"value":"0091-6749","type":"print"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A novel inhalable nanobody targeting IL-4R\u03b1 for the treatment of asthma","name":"articletitle","label":"Article Title"},{"value":"Journal of Allergy and Clinical Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaci.2024.05.027","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology","name":"copyright","label":"Copyright"}]}}