Targeting the Central Nervous System with Herpes Simplex Virus / Sleeping Beauty Hybrid Amplicon Vectors
Suresh de Silva and William J. Bowers
Affiliation: Department of Neurology, Center for Neural Development and Disease, University of Rochester Medical Center, 601 Elmwood Ave., Box 645, Rochester, NY 14642 USA.
Keywords: HSV-1, Sleeping Beauty, central nervous system, gene transfer, integration, Hybrid Amplicon Vectors, adeno-associated virus, amaurosis, RPE65 gene
The pursuits of sustainable treatments for diseases and disorders that afflict the central nervous system (CNS) have proven challenging for the field of viral vector-based gene therapy. However, recent advances in viral vector technology coupled with efficient delivery methods have opened up new avenues that show promise at the preclinical testing stage. The development of the Herpes Simplex Virus/Sleeping Beauty (HSV/SB) hybrid vector represents such an advance for devising treatments targeting the CNS with its potential for stably integrating large transgenomic segments of DNA within the genomes of transduced cells. In utero administration of this hybrid vector into the embryonic mouse brain has revealed the capacity for widespread transgene dissemination due to the targeting of a neuronal precursor cell population. This unique feature has provided the means to stably express a transgene throughout the brain for prolonged periods, which is a prerequisite for the treatment of progressive CNS disorders. In this review we provide a comprehensive breakdown of the characteristics of the HSV/SB vector system and how it can be efficiently employed in the derivation of CNStargeted gene therapeutic strategies.
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