{
  "abstract": "Background: 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 IFNB1 expression as a therapeutic strategy for DM/JDM.\n\nMethods: A library of 74 siRNAs targeting IFNB1 was designed and screened for IFNB1 knockdown by qRT-PCR. Lead siRNAs were analysed for secreted IFN beta protein reduction and acute cytotoxicity. IFNB1 expression was induced for efficacy screening in vitro , 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\nResults: 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 IFNB1 locus were screened; however, the previous lead siRNA remained the most active across relevant cell lines.\n\nConclusions: Overall, comprehensive in vitro screening identified a lead siRNA targeting IFNB1 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.",
  "abstract_shown": true,
  "affiliations": [
    "Medical Research Council Nucleic Acid Therapy Accelerator (NATA), Research Complex at Harwell , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Joanna E. Parkes"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrés F. Correa-Sánchez"
    },
    {
      "affs": [
        0
      ],
      "name": "Inês Fial"
    },
    {
      "affs": [
        0
      ],
      "name": "Isaac Tam"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaladevi Selvam"
    },
    {
      "affs": [
        0
      ],
      "name": "Mark Cunningham"
    },
    {
      "affs": [
        0
      ],
      "name": "Nick Lench"
    },
    {
      "affs": [
        0
      ],
      "name": "Peter L. Oliver"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1mvj76jjfmkx1.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1851483",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668828/?tool=EBI",
  "id": "1mvj76jjfmkx1",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13668828",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Inflammatory Myopathies and Dermatomyositis"
    ]
  ],
  "openalex": "W7215038871",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668828/pdf/?tool=EBI",
  "pmcid": "PMC13668828",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1mvj76jjfmkx1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13668828",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13668828"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1851483",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1851483/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Inflammatory Myopathies and Dermatomyositis",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Development of siRNAs targeting interferon beta as a novel therapeutic approach for adult and juvenile dermatomyositis",
  "title_text": "Development of siRNAs targeting interferon beta as a novel therapeutic approach for adult and juvenile dermatomyositis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:15Z",
  "url": "https://research.draconitic.com/paper/1mvj76jjfmkx1",
  "venue": "Frontiers in immunology",
  "versions": []
}