SGSH gene transfer in mucopolysaccharidosis type IIIA mice using canine adenovirus vectors

Lau, A. A.; Hopwood, J. J.; Kremer, E. J.; Hemsley, K. M.

Mol Genet Metab

2010-06 / vol 100 / pages 168-75


Many viral backbones have been used as gene transfer vectors. However, the efficacy of therapy based on human-derived vectors may be limited by the high incidence of pre-existing humoral and cellular memory immunity. To circumvent some of the clinical disadvantages of vectors derived from common human pathogens, we have used an E1-deleted vector derived from a xenogenic adenovirus, canine adenovirus serotype 2 (CAV-2) to ameliorate neuropathological changes associated with the lysosomal storage disorder, mucopolysaccharidosis type IIIA (MPS IIIA). This presently untreatable condition is caused by N-sulfoglucosamine sulfohydrolase (SGSH) deficiency and is characterized by heparan sulfate accumulation and progressive neurodegeneration. Injection of CAV-SGSH-GFP into the thalamus of adult MPS IIIA mouse brain resulted in short-term gene expression. In contrast, intra-ventricular injection of newborn mice yielded dose-dependent transgene expression which persisted for at least 20-weeks and improved neuropathology. Together, these studies suggest that this E1-deleted CAV-2 vector is capable of mediating regional medium-term gene expression and facilitating improvements in neuropathology in MPS IIIA mice.

Lire sur PubMed

S1096-7192(10)00054-5 [pii] 10.1016/j.ymgme.2010.02.006

1096-7206 (Electronic) 1096-7192 (Linking)


Animals; Mice; Animals, Newborn; Gene Transfer Techniques; Genetic Vectors; Adenoviruses, Canine/*genetics/immunology; Antibodies, Viral/analysis; Enzyme Replacement Therapy/*methods; Hydrolases/*therapeutic use; Mucopolysaccharidosis III/genetics/*therapy

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