Applications of adeno-associated virus vector-mediated gene delivery for neurodegenerative diseases and psychiatric diseases: Progress, advances, and challenges

Abstract

Neurodegeneration is the most common disease in the elderly population due to its slowly progressive nature of neuronal deterioration, eventually leading to executive dysfunction. The pathological markers of neurological disorders are relatively well-established, however, detailed molecular mechanisms of progression and therapeutic targets are needed to develop novel treatments in human patients. Treating known therapeutic targets of neurological diseases has been aided by recent advancements in adeno-associated virus (AAV) technology. AAVs are known for their low-immunogenicity, blood-brain barrier (BBB) penetrating ability, selective neuronal tropism, stable transgene expression, and pleiotropy. In addition, the usage of AAVs has enormous potential to be optimized. Therefore, AAV can be a powerful tool used to uncover the underlying pathophysiology of neurological disorders and to increase the success in human gene therapy. This review summarizes different optimization approaches of AAV vectors with their current applications in disease modeling, neural tracing and gene therapy, hence exploring progressive mechanisms of neurodegenerative diseases as well as effective therapy. Lastly, this review discusses the limitations and future perspectives of the AAV-mediated transgene delivery system.

Keywords: Adeno-associated virus; Gene delivery; Gene therapy; Neurodegenerative disease; Psychiatric disease.