Abstract
Neurodegenerative diseases (NDs) have a profound impact on human health worldwide and their incidence is predicted to increase as the population ages. ND severely limits the quality of life and leads to early death. Aside from treatments that may reduce symptoms, NDs are almost completely without means of therapeutic intervention. The genetic and biochemical basis of many NDs is beginning to emerge although most have complex etiologies for which common themes remain poorly resolved. Largely relying on progress in vector design, gene therapy is gaining increasing support as a strategy for genetic treatment of diseases. Here we describe recent developments in the engineering of highly defective herpes simplex virus (HSV) vectors suitable for transfer and long-term expression of large and/or multiple therapeutic genes in brain neurons in the complete absence of viral gene expression. These advanced vector platforms are safe, non-inflammatory, and persist in the nerve cell nucleus for life. In the near term, it is likely that HSV can be used to treat certain NDs that have a well-defined genetic cause. As further information on disease etiology becomes available, these vectors may take on an expanded role in ND therapies, including gene editing and repair.
Highlights
Gene Therapy Strategies, Viral Vectors and ApplicationsGene therapy is defined as a therapeutic intervention through the delivery of an exogenous gene or genes
Even diseases with known genetic causes are often accompanied by inflammatory responses that contribute to the degenerative process, and changes in metabolic processes carried out by mitochondria, for example, can directly affect neuronal cell function or viability [15,16,17]
Consistent with the results of a transfection study of individual immediate early (IE) genes [93], these results indicated that ICP4, ICP22, ICP27 and ICP0 are cytotoxic proteins that, in the absence of disabling gene mutations, will be expressed from replication-defective vectors, causing cell death
Summary
Our brain is a highly complex organ responsible for cognition, learning, memory, behavior, and movement. Some neurodegenerative diseases have a clear genetic basis, principally those caused by a single gene defect. Even diseases with known genetic causes are often accompanied by inflammatory responses that contribute to the degenerative process, and changes in metabolic processes carried out by mitochondria, for example, can directly affect neuronal cell function or viability [15,16,17]. L-DOPA to treat early-onset Parkinsonism, but fail in the long-term and do not address the fundamental disease causes Often, these treatments suffer from poor drug bioavailability due to the blood brain barrier (BBB) and may impact cells not directly involved in the disease process [18].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
