title: Targeting the central nervous system with herpes simplex virus / Sleeping Beauty hybrid amplicon vectors.
abstract: 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 CNS-targeted gene therapeutic strategies.
authors.affiliation: Department of Neurology, Center for Neural Development and Disease, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642 USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: de Silva
authors.forename: William J
authors.initials: WJ
authors.lastname: Bowers
mesh_terms: D000818:Animals; D001766:Blindness / Q000628:therapy; D001921:Brain / Q000196:embryology / Q000254:growth & development; D002493:Central Nervous System Diseases / Q000628:therapy*; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells; D018139:Simplexvirus / Q000235:genetics*; D019076:Transgenes / Q000235:genetics; D019895:Transposases / Q000235:genetics
chemical_list: D019895:Transposases; C494471:sleeping beauty transposase, human