Purewal Japneet Singh, Doshi Gaurav Mahesh
SVKM's Dr Bhanuben Nanavati College of Pharmacy, India.
SVKM's Dr Bhanuben Nanavati College of Pharmacy, India.
Eur J Pharmacol. 2024 Dec 15;985:177083. doi: 10.1016/j.ejphar.2024.177083. Epub 2024 Oct 30.
Psoriasis (Pso) is an autoimmune inflammatory skin disease characterised by well-demarcated, red plaques covered in silver scales. It affects people of all ages and can be passed down through generations. Genetics play an important role in determining vulnerability to develop Pso. Several large-scale genome-wide association studies have identified over 80 genetic loci associated with Pso susceptibility. Gene expression can be regulated via RNA interference (RNAi). RNAi suppresses gene expression by degrading mRNA molecules. Since its discovery, RNAi has generated considerable excitement over its potential therapeutic benefits. RNAi is mediated by endogenous small RNA molecules like microRNA (miRNA) or exogenous small RNA molecules like small interfering RNA (siRNA), short hairpin RNA (shRNA), and artificial micro RNA (amiRNA). These small RNA molecules can silence a disease-related gene in a sequence-specific manner. Targeting RNAi pathways can help modify disease-related biological processes in various medical conditions, including autoimmune disorders. In Pso, RNAi can downregulate the expression of molecules involved in the pathophysiology of the disease. Significant progress has been made in the field of RNAi therapeutics. However, further research is needed to fine-tune the design and delivery of RNAi therapeutics in humans. In this review, we discuss various effectors of RNAi, some challenges related to RNAi therapeutics (emphasizing siRNA) and strategies to overcome these challenges. Furthermore, we have discussed some studies that employ RNAi therapeutics for Pso.
银屑病(Psoriasis,Pso)是一种自身免疫性炎症性皮肤病,其特征为边界清晰、覆盖有银色鳞屑的红色斑块。它影响所有年龄段的人群,并且可以代代相传。遗传学在决定患银屑病的易感性方面起着重要作用。几项大规模全基因组关联研究已经确定了80多个与银屑病易感性相关的基因位点。基因表达可以通过RNA干扰(RNAi)进行调控。RNAi通过降解mRNA分子来抑制基因表达。自发现以来,RNAi因其潜在的治疗益处而引起了极大的关注。RNAi由内源性小RNA分子如微小RNA(miRNA)或外源性小RNA分子如小干扰RNA(siRNA)、短发夹RNA(shRNA)和人工微小RNA(amiRNA)介导。这些小RNA分子可以以序列特异性的方式使疾病相关基因沉默。靶向RNAi途径有助于在包括自身免疫性疾病在内的各种医学病症中改变疾病相关的生物学过程。在银屑病中,RNAi可以下调参与该疾病病理生理学的分子的表达。RNAi治疗领域已经取得了重大进展。然而,还需要进一步研究来优化RNAi治疗药物在人体中的设计和递送。在这篇综述中,我们讨论了RNAi的各种效应物、与RNAi治疗(重点是siRNA)相关的一些挑战以及克服这些挑战的策略。此外,我们还讨论了一些将RNAi治疗用于银屑病的研究。