Small interfering RNA: From designing to therapeutic in cancer

Cancer has become a significant public health concern worldwide. It is a group of diseases, often resulting from the dysregulation of multiple cellular pathways involved in differentiation, cell proliferation, cell cycle regulation, and DNA repair. These disruptions are primarily caused by genetic mutation and epigenetic alterations which lead to uncontrolled growth and tumor formation. Targeted therapy is a precise and effective strategy to overcome the shortcomings of conventional therapy. RNA interference (RNAi) is a gene-silencing mechanism that has an uncanny ability to target disease-associated genes. Small interfering RNA (siRNA) is a key component of RNAi and has shown promise in silencing oncogenes and inhibiting cancer progression. However, the therapeutic application of siRNA faces several challenges such as poor cellular uptake, short half-life, endosomal escape, immune system activation, and off-target. Strategies to address these challenges are optimized designing of siRNA, advanced delivery systems, and chemical modification to improve cellular uptake and protect from degradation. This review focuses on the therapeutic potential of siRNA in cancer treatment and discusses the action mechanism of siRNA, barriers in siRNA, and strategies to overcome them. The review shed light on the current clinical trial of siRNA-based cancer therapy, along with outcomes and limitations.