{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:00:17Z","timestamp":1790834417158,"version":"4.1.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_PC_20061"],"award-info":[{"award-number":["MC_PC_20061"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018208","name":"Cure JM Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018208","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      A key feature of the autoimmune conditions adult and juvenile dermatomyositis (DM\/JDM) is the correlation of interferon (IFN) beta induction with disease initiation and activity. Our aim was to establish a short interfering RNA (siRNA) approach to knockdown\n                      <jats:italic>IFNB1<\/jats:italic>\n                      expression as a therapeutic strategy for DM\/JDM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A library of 74 siRNAs targeting\n                      <jats:italic>IFNB1<\/jats:italic>\n                      was designed and screened for\n                      <jats:italic>IFNB1<\/jats:italic>\n                      knockdown by qRT-PCR. Lead siRNAs were analysed for secreted IFN beta protein reduction and acute cytotoxicity. IFNB1 expression was induced for efficacy screening\n                      <jats:italic>in vitro<\/jats:italic>\n                      , including in immortalised myoblasts, myotubes and dermal fibroblasts, alongside JDM patient-derived myotubes. RNA sequencing was also performed on siRNA treated and untreated dermal fibroblasts and patient myotubes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Initial screening of 27 siRNAs identified two lead siRNAs with significant knockdown of both IFN beta transcript and secreted protein in all cell lines, with one lead siRNA demonstrating a more favourable cytotoxicity profile. RNA sequencing and pathway analysis revealed that both lead siRNAs were able to reduce the induction of disease-associated immune and autoimmune pathways in dermal fibroblasts and JDM myotubes. An additional 47 siRNAs across the\n                      <jats:italic>IFNB1<\/jats:italic>\n                      locus were screened; however, the previous lead siRNA remained the most active across relevant cell lines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Overall, comprehensive\n                      <jats:italic>in vitro<\/jats:italic>\n                      screening identified a lead siRNA targeting\n                      <jats:italic>IFNB1<\/jats:italic>\n                      with significant mRNA and protein knockdown activity, low cytotoxicity and the ability to modulate immune-relevant pathways in muscle and skin cells. This is a promising first step towards the development of an siRNA therapy for DM\/JDM and other conditions driven by IFN beta over-expression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1851483","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:40:16Z","timestamp":1790833216000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of siRNAs targeting interferon beta as a novel therapeutic approach for adult and juvenile dermatomyositis"],"prefix":"10.3389","volume":"17","author":[{"given":"Joanna E.","family":"Parkes","sequence":"first","affiliation":[{"name":"Medical Research Council Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell","place":["Didcot, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s F.","family":"Correa-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Medical Research Council Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell","place":["Didcot, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas","family":"Fial","sequence":"additional","affiliation":[{"name":"Medical Research Council Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell","place":["Didcot, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Tam","sequence":"additional","affiliation":[{"name":"Medical Research Council Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell","place":["Didcot, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaladevi","family":"Selvam","sequence":"additional","affiliation":[{"name":"Medical Research Council Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell","place":["Didcot, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Medical Research Council Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell","place":["Didcot, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Lench","sequence":"additional","affiliation":[{"name":"Medical Research Council Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell","place":["Didcot, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Oliver","sequence":"additional","affiliation":[{"name":"Medical Research Council Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell","place":["Didcot, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41572-021-00321-x","article-title":"Idiopathic inflammatory myopathies","volume":"7","author":"Lundberg","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-014-0465-0","article-title":"Amyopathic dermatomyositis: definitions, diagnosis, and management","volume":"16","author":"Bailey","year":"2014","journal-title":"Curr Rheumatol Rep"},{"key":"B3","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s40674-018-0106-2","article-title":"Current treatment for myositis","volume":"4","author":"Barsotti","year":"2018","journal-title":"Curr Treatm Opt Rheumatol"},{"key":"B4","unstructured":"Corticosteroid adverse effects\n          \n          \n            \n              Yasir\n              M\n            \n            \n              Goyal\n              A\n            \n            \n              Sonthalia\n              S\n            \n          \n          Treasure Island (FL\n          StatPearls Publishing\n          Statpearls\n          \n          2026"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008128","article-title":"Identification of distinctive interferon gene signatures in different types of myositis","volume":"93","author":"Pinal-Fernandez","year":"2019","journal-title":"Neurology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2014.10.012","article-title":"Interferons as components of the complex web of reactions sustaining inflammation in idiopathic inflammatory myopathies","volume":"74","author":"De Paepe","year":"2015","journal-title":"Cytokine"},{"key":"B7","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1186\/ar2885","article-title":"Type 1 interferons and myositis","volume":"12","author":"Greenberg","year":"2010","journal-title":"Arthritis Res Ther"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20464","article-title":"Interferon-alpha\/beta-mediated innate immune mechanisms in dermatomyositis","volume":"57","author":"Greenberg","year":"2005","journal-title":"Ann Neurol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1002\/ana.21805","article-title":"Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy","volume":"67","author":"Salajegheh","year":"2010","journal-title":"Ann Neurol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1186\/ar3531","article-title":"Type I interferon pathway in adult and juvenile dermatomyositis","volume":"13","author":"Baechler","year":"2011","journal-title":"Arthritis Res Ther"},{"key":"B11","doi-asserted-by":"publisher","first-page":"59","DOI":"10.2119\/2006-00085.Baechler","article-title":"An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity","volume":"13","author":"Baechler","year":"2007","journal-title":"Mol Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2005.06786.x","article-title":"Evidence for a role of type I interferons in the pathogenesis of dermatomyositis","volume":"153","author":"Wenzel","year":"2005","journal-title":"Br J Dermatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029161","article-title":"Interferon and biologic signatures in dermatomyositis skin: specificity and heterogeneity across diseases","volume":"7","author":"Wong","year":"2012","journal-title":"PloS One"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15006","article-title":"Correlation of cutaneous disease activity with type 1 interferon gene signature and interferon \u03b2 in dermatomyositis","volume":"176","author":"Huard","year":"2017","journal-title":"Br J Dermatol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/art.40328","article-title":"Myogenic progenitor cells exhibit type I interferon-driven proangiogenic properties and molecular signature during juvenile dermatomyositis","volume":"70","author":"Gitiaux","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1731-9","article-title":"IFN-\u03b2-induced reactive oxygen species and mitochondrial damage contribute to muscle impairment and inflammation maintenance in dermatomyositis","volume":"134","author":"Meyer","year":"2017","journal-title":"Acta Neuropathol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.144.10.1341","article-title":"Severe dermatomyositis triggered by interferon beta-1a therapy and associated with enhanced type I interferon signaling","volume":"144","author":"Somani","year":"2008","journal-title":"Arch Dermatol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1071","article-title":"Ensembl 2025","volume":"53","author":"Dyer","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/s41392-020-0207-x","article-title":"Therapeutic siRNA: state of the art","volume":"5","author":"Hu","year":"2020","journal-title":"Sig Transduct Target Ther"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/35078107","article-title":"Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells","volume":"411","author":"Elbashir","year":"2001","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-022-00549-3","article-title":"Therapeutic siRNA: State-of-the-art and future perspectives","volume":"36","author":"Friedrich","year":"2022","journal-title":"BioDrugs"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1307-8_22","article-title":"iDEP web application for RNA-Seq data analysis","volume":"2284","author":"Ge","year":"2021","journal-title":"Methods Mol Biol"},{"key":"B23","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"Ggplot2: Elegant Graphics for Data Analysis","author":"Wickham","year":"2016"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1177\/1753425912459975","article-title":"TLR3 activation efficiency by high or low molecular mass poly I:C","volume":"19","author":"Zhou","year":"2013","journal-title":"Innate Immun"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.237","article-title":"Type I interferons: crucial participants in disease amplification in autoimmunity","volume":"6","author":"Hall","year":"2010","journal-title":"Nat Rev Rheumatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/hxin6o","article-title":"Use of Janus kinase inhibitors in dermatomyositis: a systematic literature review","volume":"41","author":"Paik","year":"2023","journal-title":"Clin Exp Rheumatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae909","article-title":"KEGG: biological systems database as a model of the real world","volume":"53","author":"Kanehisa","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst"},{"key":"B29","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13075-020-02160-9","article-title":"Expression of interferon-regulated genes in juvenile dermatomyositis versus Mendelian autoinflammatory interferonopathies","volume":"22","author":"Kim","year":"2020","journal-title":"Arthritis Res Ther"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ard.2025.07.015","article-title":"Spatial transcriptomic analysis of muscle biopsy from patients with treatment-naive juvenile dermatomyositis reveals mitochondrial abnormalities despite disease-related interferon-driven signature","volume":"84","author":"Syntakas","year":"2025","journal-title":"Ann Rheum Dis"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.03.002","article-title":"New insights into type I interferon and the immunopathogenesis of persistent viral infections","volume":"34","author":"Snell","year":"2015","journal-title":"Curr Opin Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.05.005","article-title":"Type I interferon in chronic virus infection and cancer","volume":"38","author":"Snell","year":"2017","journal-title":"Trends Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-023-01361-4","article-title":"Innate immune regulations and various siRNA modalities","volume":"13","author":"Kaushal","year":"2023","journal-title":"Drug Delivery Transl Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/978-1-0716-4742-4_2","article-title":"Molecular mechanisms of innate immune sensing of exogenous RNAs","volume":"2965","author":"Sioud","year":"2025","journal-title":"Methods Mol Biol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2024.102437","article-title":"Development, opportunities, and challenges of siRNA nucleic acid drugs","volume":"36","author":"Xiao","year":"2025","journal-title":"Mol Ther Nucleic Acids"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-00912-9","article-title":"RNAi-based drug design: considerations and future directions","volume":"23","author":"Tang","year":"2024","journal-title":"Nat Rev Drug Discov"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-024-01164-7","article-title":"Recent updates on the pathogenesis of inflammatory myopathies","volume":"26","author":"Musai","year":"2024","journal-title":"Curr Rheumatol Rep"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.70130","article-title":"The safety and efficacy of JAK inhibitors: Have we found the right pathway","volume":"28","author":"Wang","year":"2025","journal-title":"Int J Rheum Dis"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1445680","article-title":"Use of Janus kinase inhibitors before and after European Medicines Agency safety recommendations: a retrospective study","volume":"15","author":"Strunz","year":"2024","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)02071-3","article-title":"Efficacy, safety, and target engagement of dazukibart, an IFN\u03b2 specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial","volume":"405","author":"Fiorentino","year":"2025","journal-title":"Lancet"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.70059","article-title":"Dazukibart for the treatment of severe TIF1\u03b3-positive juvenile dermatomyositis","volume":"40","author":"Fournier","year":"2026","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaf549","article-title":"IFN-\u03b1 levels correlate with muscle disease activity only in juvenile dermatomyositis patients with anti-MDA5+ autoantibodies","volume":"65","author":"Moreau","year":"2026","journal-title":"Rheumatol (Oxford)"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-8585com","article-title":"A structural basis for interferon-alpha-receptor interactions","volume":"21","author":"Kumaran","year":"2007","journal-title":"FASEB J"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2011.109","article-title":"Expression profiles of human interferon-alpha and interferon-lambda subtypes are ligand- and cell-dependent","volume":"90","author":"Hillyer","year":"2012","journal-title":"Immunol Cell Biol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2009.07.005","article-title":"The role of differential expression of human interferon--a genes in antiviral immunity","volume":"20","author":"G\u00e9nin","year":"2009","journal-title":"Cytokine Growth Factor Rev"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad415","article-title":"Targeted tissue delivery of RNA therapeutics using antibody-oligonucleotide conjugates (AOCs)","volume":"51","author":"Malecova","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf270","article-title":"Conjugation to a transferrin receptor 1-binding Bicycle peptide enhances ASO and siRNA potency in skeletal and cardiac muscles","volume":"53","author":"\u00d8stergaard","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-025-01376-x","article-title":"siRNA conjugate with high albumin affinity and degradation resistance for delivery and treatment of arthritis in mice and Guinea pigs","volume":"9","author":"Colazo","year":"2025","journal-title":"Nat BioMed Eng"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.12.009","article-title":"Transdermal delivery of Fn14 siRNA using a novel composite ionic liquid for treatment of psoriasis-like skin lesions","volume":"365","author":"Li","year":"2024","journal-title":"J Control Release"},{"key":"B50","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1038\/s41467-026-68993-1","article-title":"Intradermal delivery of lipophilic siRNAs enables prolonged skin retention and sustained gene silencing in a porcine model","volume":"17","author":"Fakih","year":"2026","journal-title":"Nat Commun"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1177\/09733698251405036","article-title":"Juvenile dermatomyositis: An update of the immunopathogenesis, clinical features, and management","volume":"21","author":"Basu","year":"2026","journal-title":"Indian J Rheumatol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2024.09.017","article-title":"Recent advances in juvenile dermatomyositis: Moving toward integration of myositis-specific antibody clinical phenotypes, IFN-driven pathogenesis, and targeted therapies","volume":"145","author":"Chen","year":"2025","journal-title":"J Invest Dermatol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/art.22558","article-title":"Plasmacytoid dendritic cells in inflamed muscle of patients with juvenile dermatomyositis","volume":"56","author":"L\u00f3pez de Padilla","year":"2007","journal-title":"Arthritis Rheum"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107469","article-title":"Overcoming limitations and advancing the therapeutic potential of antibody-oligonucleotide conjugates (AOCs): Current status and future perspectives","volume":"209","author":"Jiao","year":"2024","journal-title":"Pharmacol Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00633-9","article-title":"The type I interferonopathies: 10 years on","volume":"22","author":"Crow","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.63966","article-title":"Evaluation of the efficacy and safety of Anifrolumab in moderate-to-severe systemic lupus erythematosus","volume":"16","author":"Cingireddy","year":"2024","journal-title":"Cureus"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1851483\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:40:19Z","timestamp":1790833219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1851483\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":56,"alternative-id":["10.3389\/fimmu.2026.1851483"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1851483","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"article-number":"1851483"}}