Widespread Correction of Lysosomal Storage in the Mucopolysaccharidosis Type VII Mouse Brain with a Herpes Simplex Virus Type 1 Vector Expressing β-Glucuronidase
| Autor: | Bradford K. Berges, Richard R. Miselis, John H. Wolfe, Srikanth Yellayi, Nigel W. Fraser, Brian A. Karolewski |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Anatomic Mucopolysaccharidosis Thalamus Genetic Vectors Hippocampus Substantia nigra Mucopolysaccharidosis VII Herpesvirus 1 Human Biology 03 medical and health sciences Mice 0302 clinical medicine Chlorocebus aethiops Drug Discovery medicine Lysosomal storage disease Genetics Animals Tissue Distribution Vero Cells Molecular Biology 030304 developmental biology Glucuronidase Pharmacology 0303 health sciences Mice Inbred C3H Brain Genetic Therapy medicine.disease Virology Molecular biology Mice Mutant Strains 3. Good health medicine.anatomical_structure nervous system Cerebral cortex Axoplasmic transport Molecular Medicine Female Lysosomes 030217 neurology & neurosurgery |
| Zdroj: | Molecular Therapy. 13(5):859-869 |
| ISSN: | 1525-0016 |
| DOI: | 10.1016/j.ymthe.2005.12.017 |
| Popis: | 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 correction of lysosomal storage diseases with HSV-1 vectors is discussed. |
| Databáze: | OpenAIRE |
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