Widespread correction of lysosomal storage in the mucopolysaccharidosis type VII mouse brain with a herpes simplex virus type 1 vector expressing beta-glucuronidase

Molecular Therapy : the Journal of the American Society of Gene Therapy
Bradford K BergesNigel W Fraser

Abstract

We have inoculated a herpes simplex virus type 1 (HSV-1) vector into a variety of sites in the mouse brain and assayed the regions of latency and expression of a beta-glucuronidase (GUSB) cDNA from the latency-associated transcript promoter. Injection sites used were somatosensory cortex, visual cortex, striatum, dorsal hippocampus, and CSF spaces. Latent vector was detected in regions at a distance from the respective injection sites, consistent with axonal transport of vector. Regions of GUSB activity varied by injection site and included cerebral cortex, striatum, thalamus, hypothalamus, substantia nigra, hippocampus, midbrain, pons, medulla, cerebellum, and spinal cord. After a single injection, GUSB enzymatic activity reached wild-type levels in several brain regions. GUSB was found in some areas without any detectable vector, indicative of axonal transport of GUSB enzyme. GUSB-deficient mice, which have the lysosomal storage disease mucopolysaccharidosis (MPS) VII, have lysosomal storage lesions in cells throughout the brain. Adult MPS VII mice treated by injection of vector into a single site on each side of the brain had correction of storage lesions in a large volume of brain. The potential for long-term, widespread co...Continue Reading

References

Mar 1, 1992·The Journal of Cell Biology·M T ShiehP G Spear
Dec 1, 1996·Acta Neuropathologica·B LevyW S Sly
Jan 26, 1999·JAMA : the Journal of the American Medical Association·P J MeikleW F Carey
Jan 12, 2000·Experimental Neurology·J H KordowerP Aebischer
Aug 10, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·A BoschJ M Heard
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Andrew I BrooksBeverly L Davidson
Jan 15, 2003·Clinical Microbiology Reviews·Clinton Jones
Sep 23, 2003·Gene Therapy·Charles H ViteJohn H Wolfe
Oct 14, 2003·Experimental Neurology·John H RogersStacey Efstathiou
May 11, 2004·The Journal of Gene Medicine·N Matthew EllinwoodMark E Haskins
Oct 19, 2004·Annual Review of Microbiology·Joseph C Glorioso, David J Fink
Aug 27, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·B K BergesN W Fraser

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Citations

Apr 24, 2013·Nature Reviews. Neurology·Michele SimonatoJoseph C Glorioso
Dec 14, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Bradford K BergesNigel W Fraser
Aug 31, 2007·Expert Opinion on Biological Therapy·Katherine P Ponder, Mark E Haskins
Nov 19, 2015·Journal of Inherited Metabolic Disease·Shunji TomatsuMarta Serafini

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