[Frontiers in Bioscience E5, 188-203, January 1, 2013]

Gene delivery with viral vectors for cerebrovascular diseases

Yu Gan1,2, Zheng Jing1,2, R. Anne Stetler1,2, Guodong Cao1,2

1Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA 15240, U.S.A.; 2Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, U.S.A.

TABLE OF CONTENTS 1. Abstract

2. Introduction
3. Viral vector-based gene delivery into the CNS
3.1. Lentiviral vectors
3.2. Adenoviral vectors
3.3. Adeno-associated viral (AAV) vector
3.4. Herpes simplex virus
3.5. Promoter effects on viral vector-mediated transgene expression
4. Cerebrovascular diseases
4.1. Ischemic stroke
4.1.1. HSV vectors
4.1.2. AAV vectors
4.1.3. Lentiviral vectors
4.1.4. RNA interference
4.1.5. Global cerebral ischemia
4.2. Hemorrhagic stroke
4.3. Subarachnoid hemorrhage
5. Non-viral gene delivery compared to viral vector
6. Summary
7. Acknowledgments
8. References

1. ABSTRACT

Recent achievements in the understanding of molecular events involved in the pathogenesis of central nervous system (CNS) injury have made gene transfer a promising approach for various neurological disorders, including cerebrovascular diseases. However, special obstacles, including the post-mitotic nature of neurons and the blood-brain barrier (BBB), constitute key challenges for gene delivery to the CNS. Despite the various limitations in current gene delivery systems, a spectrum of viral vectors has been successfully used to deliver genes to the CNS. Furthermore, recent advancements in vector engineering have improved the safety and delivery of viral vectors. Numerous viral vector-based clinical trials for neurological disorders have been initiated. This review will summarize the current implementation of viral gene delivery in the context of cerebrovascular diseases including ischemic stroke, hemorrhagic stroke and subarachnoid hemorrhage (SAH). In particular, we will discuss the potentially feasible ways in which viral vectors can be manipulated and exploited for use in neural delivery and therapy.