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

Adeline A. Lau, John J. Hopwood, Eric J. Kremer, Kim M. Hemsley

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26 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)168-175
Number of pages8
JournalMolecular Genetics and Metabolism
Issue number2
Publication statusPublished - Jun 2010
Externally publishedYes


  • Canine adenovirus
  • Gene therapy
  • Mucopolysaccharidosis
  • Sanfilippo syndrome


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