Advancements in Gene Delivery using Nucleic Acid Loaded Nanoparticles for Region Specific Delivery in Alzheimer's...

Alzheimer's disease (AD) is a progressive and the most common neurodegenerative condition, having a deleterious effect on memory, eventually leading to death. In the recent past, gene therapy has emerged as a promising and revolutionary treatment for AD. This study demonstrated that nucleic acid-loaded nanoparticles which deliver small interfering RNA through lipid nanoparticles successfully reduced Alzheimer's disease-related symptoms in preclinical models by decreasing amyloid-β levels and enhancing cognitive abilities. However, every rose has its thorn, as the output of gene therapy is considerably hampered by the physiological barriers of the brain, which include the blood-brain barrier and the brain's extracellular matrix (ECM). For this reason, many researchers have modified the gene delivery technique by developing 'brain penetrating' NPs coated with components that can prevent sticking to the ECM. Moreover, to overcome the challenge of low transgene expression and reduced accumulation in the brain, even when delivered at high doses, scientists have proposed that injection/delivery of gene vectors directly into a specific area in the brain can achieve maximum therapeutic efficacy. Hence, this review focuses on the advancements and advantages of region-specific delivery of nucleic acid-loaded NPs for the effective therapeutic management of AD.