Psoriasis is a chronic autoimmune disease of the skin manifested by keratinocyte hyperproliferation, immune dysregulation, and chronic inflammation that result in scaly plaques. Conventional interventions such as corticosteroids, immunosuppressants, and biologics offer symptomatic relief but are limited by side effects and incomplete remission. Psoriasis pathogenesis is complex and entails numerous immune cells (dendritic cells, Th1, Th17, Th22, Tregs, macrophages, NK cells) and molecular pathways (IL-17, IL-22, IL-23, TNF-α, NF-κB). Gene therapy suppresses cytokine production, modulates immune activation, and normalizes keratinocyte turnover to achieve sustained control of disease. Gene therapy is a promising option by modulating inflammatory circuits at the molecular level. Methods such as CRISPR-Cas9, RNA interference (RNAi), and antisense oligonucleotides (ASOs) target major psoriasis-related cytokines (IL-17, IL-22, IL-23, TNF-α) and transcription factors (NF-κB), inhibiting inflammation and abnormal keratinocyte proliferation. With ongoing research, gene-based therapies in combination with biologics and nanotechnology-based drug delivery provide a personalized and efficient option for the treatment of psoriasis. This review discusses conventional and innovative gene therapies, which have been found to hit specific cellular and molecular targets to combat psoriasis therapy.
