Characterization of a Novel Mucopolysaccharidosis Type II Mouse Model and Recombinant AAV2/8 Vector-Mediated Gene Therapy

다국어 초록 (Multilingual Abstract)

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked inherited disorder caused by a deficiency of the enzyme iduronate-2-sulfatase (IDS), which results in the lysosomal accumulation of glycosaminoglycans (GAG) such as dermatan and heparan sulfate. Here, we report the generation of IDS knockout mice, a model of human MPS II, and an analysis of the resulting phenotype. We also evalu-ated the effect of gene therapy with a pseudotyped, re-combinant adeno-associated virus 2/8 vector encoding the human IDS gene (rAAV-hIDS) in IDS-deficient mice. IDS activity and GAG levels were measured in serum and tis-sues after therapy. Gene therapy completely restored IDS activity in plasma and tissue of the knockout mice. The rescued enzymatic activity completely cleared the accu-mulated GAGs in all the tissues analyzed. This model can be used to explore the therapeutic potential of IDS re-placement and other strategies for the treatment of MPS II. Additionally, AAV2/8 vectors have promising future clinical applications for the treatment of patients with MPS II.

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