Journal
GENE THERAPY
Volume 10, Issue 22, Pages 1874-1881Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gt.3302087
Keywords
AAV; feline; animal model; central nervous system
Categories
Funding
- NCRR NIH HHS [RR02512] Funding Source: Medline
- NIDDK NIH HHS [DK49652, DK63973, DK07748, R01 DK063973, DK47747] Funding Source: Medline
- NIH HHS [P40 OD010939] Funding Source: Medline
- NINDS NIH HHS [K08 NS02032, R01 NS038690, NS38690] Funding Source: Medline
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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 beta-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 AAV1 vector resulted in greater transduction of the gray matter than AAV2 as well as transduction of the white matter. AAV5 did not result in detectable transduction in the cat brain.
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