Unlocking therapeutic potential of siRNA-based drug delivery system for treatment of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of amyloid-beta (Aβ) plaques and tau tangles, leading to cognitive decline and neuronal loss. While current treatments mainly provide symptomatic relief, they do not target the underlying molecular causes of the disease. In recent years, RNA interference (RNAi), particularly small interfering RNA (siRNA), has emerged as a promising therapeutic approach for AD. siRNA works by selectively silencing genes responsible for disease processes, degrading messenger RNA (mRNA) and preventing protein synthesis. In AD, siRNA is used to target key pathological factors, such as beta-secretase 1 (BACE1), tau protein, and pro-inflammatory cytokines, to reduce Aβ production, preventing tau hyperphosphorylation, and mitigating neuroinflammation. Preclinical studies in animal models have shown promising results, including significant reductions in Aβ levels and improved cognitive function following siRNA delivery. However, several challenges remain in translating siRNA-based therapies to clinical use, including efficient delivery across the blood-brain barrier (BBB), minimizing off-target effects, and ensuring prolonged gene silencing with minimal immune activation. To overcome these barriers, innovative delivery methods are being explored, such as lipid nanoparticles (LNPs), exosomes, and viral vectors, which aim to improve the stability, specificity, and efficiency of siRNA therapies. Despite these challenges, recent advances in siRNA design and delivery technologies hold great promise, offering a potential new approach to modifying the course of AD and providing hope for more effective, disease-modifying treatments.