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Mol. Cells 2010; 30(1): 13-18

Published online July 31, 2010

https://doi.org/10.1007/s10059-010-0083-2

© The Korean Society for Molecular and Cellular Biology

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

Sung-Chul Jung1, Eun-Sook Park1, Eun Nam Choi1, Chi Hwa Kim2, Su Jin Kim, and Dong-Kyu Jin*

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea, 1Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul 158-710, Korea, 2Clinical Research Center, Samsung Biomedical Research Institute, Seoul 135-710, Korea

Correspondence to : *Correspondence: jindk@skku.edu

Received: November 6, 2010; Revised: April 20, 2010; Accepted: April 20, 2010

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 evaluated the effect of gene therapy with a pseudotyped, recombinant 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 tissues after therapy. Gene therapy completely restored IDS activity in plasma and tissue of the knockout mice. The rescued enzymatic activity completely cleared the accumulated GAGs in all the tissues analyzed. This model can be used to explore the therapeutic potential of IDS replacement 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.

Keywords adeno-associated virus, gene therapy, hunter syndrome, iduronate-2-sulfatase, MPS II mouse model

Article

Research Article

Mol. Cells 2010; 30(1): 13-18

Published online July 31, 2010 https://doi.org/10.1007/s10059-010-0083-2

Copyright © The Korean Society for Molecular and Cellular Biology.

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

Sung-Chul Jung1, Eun-Sook Park1, Eun Nam Choi1, Chi Hwa Kim2, Su Jin Kim, and Dong-Kyu Jin*

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea, 1Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul 158-710, Korea, 2Clinical Research Center, Samsung Biomedical Research Institute, Seoul 135-710, Korea

Correspondence to:*Correspondence: jindk@skku.edu

Received: November 6, 2010; Revised: April 20, 2010; Accepted: April 20, 2010

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 evaluated the effect of gene therapy with a pseudotyped, recombinant 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 tissues after therapy. Gene therapy completely restored IDS activity in plasma and tissue of the knockout mice. The rescued enzymatic activity completely cleared the accumulated GAGs in all the tissues analyzed. This model can be used to explore the therapeutic potential of IDS replacement 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.

Keywords: adeno-associated virus, gene therapy, hunter syndrome, iduronate-2-sulfatase, MPS II mouse model

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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