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Adeno-associated virus vector-mediated transduction in the cat brain

Identifieur interne : 001874 ( Main/Exploration ); précédent : 001873; suivant : 001875

Adeno-associated virus vector-mediated transduction in the cat brain

Auteurs : Charles H. Vite [États-Unis] ; Marco A. Passini [États-Unis] ; Mark E. Haskins [États-Unis] ; John H. Wolfe [États-Unis]

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RBID : Pascal:04-0174547

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English descriptors

Abstract

Adeno-associated virus (AAV) vectors are capable of delivering a therapeutic gene to the mouse brain that can result in long-term and widespread protein production. However, the human infant brain is more than 1000 times larger than the mouse brain, which will make the treatment of global neurometabolic disorders in children more difficult. In this study, we evaluated the ability of three AAV serotypes (1,2, and 5) to transduce cells in the cat brain as a model of a large mammalian brain. The human lysosomal enzyme β-glucuronidase (GUSB) was used as a reporter gene, because it can be distinguished from feline GUSB by heat stability. The vectors were injected into the cerebral cortex, caudate nucleus, thalamus, corona radiata, internal capsule, and centrum semiovale of 8-week-old cats. The brains were evaluated for gene expression using in situ hybridization and enzyme histochemistry 10 weeks after surgery. The AAV2 vector was capable of transducing cells in the gray matter, while the AA V1 vector resulted in greater transduction of the gray matter than AA V2 as well as transduction of the white matter. AAV5 did not result in detectable transduction in the cat brain.


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<div type="abstract" xml:lang="en">Adeno-associated virus (AAV) vectors are capable of delivering a therapeutic gene to the mouse brain that can result in long-term and widespread protein production. However, the human infant brain is more than 1000 times larger than the mouse brain, which will make the treatment of global neurometabolic disorders in children more difficult. In this study, we evaluated the ability of three AAV serotypes (1,2, and 5) to transduce cells in the cat brain as a model of a large mammalian brain. The human lysosomal enzyme β-glucuronidase (GUSB) was used as a reporter gene, because it can be distinguished from feline GUSB by heat stability. The vectors were injected into the cerebral cortex, caudate nucleus, thalamus, corona radiata, internal capsule, and centrum semiovale of 8-week-old cats. The brains were evaluated for gene expression using in situ hybridization and enzyme histochemistry 10 weeks after surgery. The AAV2 vector was capable of transducing cells in the gray matter, while the AA V1 vector resulted in greater transduction of the gray matter than AA V2 as well as transduction of the white matter. AAV5 did not result in detectable transduction in the cat brain.</div>
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