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Pike, L.S.* ; Tannous, B.A.* ; Deliolanis, N.C. ; Hsich, G.* ; Morse, D.* ; Tung, C.H.* ; Sena-Esteves, M.* ; Breakefield, X.O.*

Imaging gene delivery in a mouse model of congenital neuronal ceroid lipofuscinosis.

Gene Ther. 18, 1173-1178 (2011)
Open Access Green as soon as Postprint is submitted to ZB.
Adeno-associated virus (AAV)-mediated gene replacement for lysosomal disorders have been spurred by the ability of some serotypes to efficiently transduce neurons in the brain and by the ability of lysosomal enzymes to cross-correct among cells. Here, we explored enzyme replacement therapy in a knock-out mouse model of congenital neuronal ceroid lipofuscinosis (NCL), the most severe of the NCLs in humans. The missing protease in this disorder, cathepsin D (CathD) has high levels in the central nervous system. This enzyme has the potential advantage for assessing experimental therapy in that it can be imaged using a near-infrared fluorescence (NIRF) probe activated by CathD. Injections of an AAV2/rh8 vector-encoding mouse CathD (mCathD) into both cerebral ventricles and peritoneum of newborn knock-out mice resulted in a significant increase in lifespan. Successful delivery of active CathD by the AAV2/rh8-mCathD vector was verified by NIRF imaging of mouse embryonic fibroblasts from knock-out mice in culture, as well as by ex vivo NIRF imaging of the brain and liver after gene transfer. These studies support the potential effectiveness and imaging evaluation of enzyme replacement therapy to the brain and other organs in CathD null mice via AAV-mediated gene delivery in neonatal animals.
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Publication type Article: Journal article
Document type Scientific Article
Keywords fluorescence; lysosomal storage disease; cathepsin D; central nervous system; AAV; neurologic disease
ISSN (print) / ISBN 0969-7128
e-ISSN 1476-5462
Journal Gene Therapy
Quellenangaben Volume: 18, Issue: 12, Pages: 1173-1178 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed