Image 1_Development of siRNAs targeting interferon beta as a novel therapeutic approach for adult and juvenile dermatomyositis.tif

Our aim was to establish a short interfering RNA (siRNA) approach to knockdown IFNB1 expression as a therapeutic strategy for DM/JDM.</p>Methods<p>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.</p>Results<p>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.