{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:01:45Z","timestamp":1792450905796,"version":"4.5.0"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:00:00Z","timestamp":1557187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006400","name":"Alnylam Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006400","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy - Methods & Clinical Development"],"published-print":{"date-parts":[[2019,6]]},"DOI":"10.1016\/j.omtm.2019.04.009","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T22:50:40Z","timestamp":1557442240000},"page":"484-492","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":56,"special_numbering":"C","title":["Investigational RNAi Therapeutic Targeting C5 Is Efficacious in Pre-clinical Models of Myasthenia Gravis"],"prefix":"10.1016","volume":"13","author":[{"given":"Linda L.","family":"Kusner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Yucius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjistha","family":"Sengupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Sprague","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhruv","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuyen","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Charisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satya","family":"Kuchimanchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev","family":"Kallanthottathil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Fitzgerald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry J.","family":"Kaminski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Borodovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2019.04.009_bib1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.revmed.2013.09.012","article-title":"[Myasthenia gravis and autoantibodies: Pathophysiology of the different subtypes]","volume":"35","author":"Berrih-Aknin","year":"2014","journal-title":"Rev. Med. Interne"},{"key":"10.1016\/j.omtm.2019.04.009_bib2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1097\/00005072-197803000-00008","article-title":"Ultrastructural localization of immune complexes (IgG and C3) at the end-plate in experimental autoimmune myasthenia gravis","volume":"37","author":"Sahashi","year":"1978","journal-title":"J.\u00a0Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.omtm.2019.04.009_bib3","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/00005072-198003000-00005","article-title":"Ultrastructural localization of the terminal and lytic ninth complement component (C9) at the motor end-plate in myasthenia gravis","volume":"39","author":"Sahashi","year":"1980","journal-title":"J.\u00a0Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.omtm.2019.04.009_bib4","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1212\/WNL.43.6.1167","article-title":"Myasthenia gravis: quantitative immunocytochemical analysis of inflammatory cells and detection of complement membrane attack complex at the end-plate in 30 patients","volume":"43","author":"Nakano","year":"1993","journal-title":"Neurology"},{"key":"10.1016\/j.omtm.2019.04.009_bib5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.expneurol.2015.03.010","article-title":"Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors: Recommendations for methods and experimental designs","volume":"270","author":"Losen","year":"2015","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.omtm.2019.04.009_bib6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.expneurol.2015.02.025","article-title":"Guidelines for pre-clinical assessment of the acetylcholine receptor: specific passive transfer myasthenia gravis model. Recommendations for methods and experimental designs","volume":"270","author":"Kusner","year":"2015","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.omtm.2019.04.009_bib7","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1084\/jem.147.4.973","article-title":"Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis","volume":"147","author":"Lennon","year":"1978","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.omtm.2019.04.009_bib8","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.4049\/jimmunol.140.8.2589","article-title":"C5 gene influences the development of murine myasthenia gravis","volume":"140","author":"Christadoss","year":"1988","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.omtm.2019.04.009_bib9","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.4049\/jimmunol.171.7.3847","article-title":"Genetic evidence for involvement of classical complement pathway in induction of experimental autoimmune myasthenia gravis","volume":"171","author":"T\u00fcz\u00fcn","year":"2003","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.omtm.2019.04.009_bib10","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/j.1365-2249.2006.03198.x","article-title":"Complement membrane attack is required for endplate damage and clinical disease in passive experimental myasthenia gravis in Lewis rats","volume":"146","author":"Chamberlain-Banoub","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"10.1016\/j.omtm.2019.04.009_bib11","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1172\/JCI0216086","article-title":"Markedly enhanced susceptibility to experimental autoimmune myasthenia gravis in the absence of decay-accelerating factor protection","volume":"110","author":"Lin","year":"2002","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.omtm.2019.04.009_bib12","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.expneurol.2006.06.003","article-title":"Deficiency of decay accelerating factor and CD59 leads to crisis in experimental myasthenia","volume":"202","author":"Kaminski","year":"2006","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.omtm.2019.04.009_bib13","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/mus.23448","article-title":"Cell surface complement regulators moderate experimental myasthenia gravis pathology","volume":"47","author":"Kusner","year":"2013","journal-title":"Muscle Nerve"},{"key":"10.1016\/j.omtm.2019.04.009_bib14","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1002\/mus.23247","article-title":"Protective effect of scFv-DAF fusion protein on the complement attack to acetylcholine receptor: a possible option for treatment of myasthenia gravis","volume":"45","author":"Song","year":"2012","journal-title":"Muscle Nerve"},{"key":"10.1016\/j.omtm.2019.04.009_bib15","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/mus.24057","article-title":"Targeting therapy to the neuromuscular junction: proof of concept","volume":"49","author":"Kusner","year":"2014","journal-title":"Muscle Nerve"},{"key":"10.1016\/j.omtm.2019.04.009_bib16","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jaut.2013.01.003","article-title":"Complement C2 siRNA mediated therapy of myasthenia gravis in mice","volume":"42","author":"Huda","year":"2013","journal-title":"J.\u00a0Autoimmun."},{"key":"10.1016\/j.omtm.2019.04.009_bib17","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.4049\/jimmunol.142.8.2654","article-title":"Inhibition of acute passive transfer experimental autoimmune myasthenia gravis with Fab antibody to complement C6","volume":"142","author":"Biesecker","year":"1989","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.omtm.2019.04.009_bib18","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0165-5728(96)00144-0","article-title":"Soluble complement receptor 1 (sCR1) protects against experimental autoimmune myasthenia gravis","volume":"71","author":"Piddlesden","year":"1996","journal-title":"J.\u00a0Neuroimmunol."},{"key":"10.1016\/j.omtm.2019.04.009_bib19","doi-asserted-by":"crossref","first-page":"8562","DOI":"10.4049\/jimmunol.179.12.8562","article-title":"Anti-C5 antibody treatment ameliorates weakness in experimentally acquired myasthenia gravis","volume":"179","author":"Zhou","year":"2007","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.omtm.2019.04.009_bib20","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/ana.21536","article-title":"Novel complement inhibitor limits severity of experimentally myasthenia gravis","volume":"65","author":"Soltys","year":"2009","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.omtm.2019.04.009_bib21","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/S1474-4422(17)30369-1","article-title":"Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study","volume":"16","author":"Howard","year":"2017","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.omtm.2019.04.009_bib22","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/mus.23839","article-title":"A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis","volume":"48","author":"Howard","year":"2013","journal-title":"Muscle Nerve"},{"key":"10.1016\/j.omtm.2019.04.009_bib23","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nrneph.2014.30","article-title":"Anaemia: mutations in C5 explain eculizumab resistance","volume":"10","author":"Razzak","year":"2014","journal-title":"Nat. Rev. Nephrol."},{"key":"10.1016\/j.omtm.2019.04.009_bib24","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1056\/NEJMoa1311084","article-title":"Genetic variants in C5 and poor response to eculizumab","volume":"370","author":"Nishimura","year":"2014","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.omtm.2019.04.009_bib25","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1758-907X-1-14","article-title":"A status report on RNAi therapeutics","volume":"1","author":"Vaishnaw","year":"2010","journal-title":"Silence"},{"key":"10.1016\/j.omtm.2019.04.009_bib26","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0140-6736(13)61914-5","article-title":"Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin\/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial","volume":"383","author":"Fitzgerald","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.omtm.2019.04.009_bib27","doi-asserted-by":"crossref","first-page":"16958","DOI":"10.1021\/ja505986a","article-title":"Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing","volume":"136","author":"Nair","year":"2014","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.omtm.2019.04.009_bib28","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1056\/NEJMoa1208760","article-title":"Safety and efficacy of RNAi therapy for transthyretin amyloidosis","volume":"369","author":"Coelho","year":"2013","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.omtm.2019.04.009_bib29","doi-asserted-by":"crossref","first-page":"12062","DOI":"10.1073\/pnas.211257298","article-title":"Extraocular muscle is defined by a fundamentally distinct gene expression profile","volume":"98","author":"Porter","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2019.04.009_bib30","doi-asserted-by":"crossref","first-page":"4348","DOI":"10.1167\/iovs.14-14422","article-title":"RNA expression analysis of passive transfer myasthenia supports extraocular muscle as a unique immunological environment","volume":"55","author":"Zhou","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.omtm.2019.04.009_bib31","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1182\/blood-2011-06-359646","article-title":"Design and development of TT30, a novel C3d-targeted C3\/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases","volume":"118","author":"Fridkis-Hareli","year":"2011","journal-title":"Blood"}],"container-title":["Molecular Therapy - Methods & Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050119300452?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050119300452?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:27:06Z","timestamp":1762421226000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2329050119300452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6]]},"references-count":31,"alternative-id":["S2329050119300452"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2019.04.009","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2019,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Investigational RNAi Therapeutic Targeting C5 Is Efficacious in Pre-clinical Models of Myasthenia Gravis","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy - Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2019.04.009","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors.","name":"copyright","label":"Copyright"}]}}