Transduction of neurons lining the cerebral external capsules in mice with feline immunodeficiency virus based...

Gene therapy in the brain has focused mainly on neurons (gray matter), with little comparable research on white matter. In this study, injections into mice cerebral white matter of mice were done to assess the distribution of gene transfer with recombinant feline immunodeficiency virus vectors expressing either beta-galactosidase or beta-glucuronidase. Our results show that vectors were preferentially distributed along the white matter of the external capsule, which was the site of vector injection as confirmed by horseradish peroxidase labeling. Moreover, we found gene transfer almost exclusively to NeuN(+) cells lining the external capsule, which then robustly secreted recombinant beta-glucuronidase throughout the white matter of the entire external capsule on the injected side. These results may have application to lysosomal storage diseases with widespread central nervous system deficits, and other disorders such as multiple sclerosis and human immunodeficiency virus dementia.