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Type: Journal article
Title: Lentiviral-mediated correction of MPS VI cells and gene transfer to joint tissues
Author: Byers, S.
Rothe, M.
Lalic, J.
Koldej, R.
Anson, D.
Citation: Molecular Genetics and Metabolism, 2009; 97(2):102-108
Publisher: Academic Press Inc Elsevier Science
Issue Date: 2009
ISSN: 1096-7192
Statement of
Sharon Byers, Miriam Rothe, Jelena Lalic, Rachel Koldej and Donald S. Anson
Abstract: Joint disease in mucopolysaccharidosis type VI (MPS VI) remains difficult to treat despite the success of enzyme replacement therapy in treating other symptoms. In this study, the efficacy of a lentiviral vector to transduce joint tissues and express N-acetylgalactosamine-4-sulphatase (4S), the enzyme deficient in MPS VI, was evaluated in vitro and the expression of beta-galactosidase was used to evaluate transduction in vivo. High viral copy number was achieved in MPS VI fibroblasts and 4-sulphatase activity reached 12 times the normal level. Storage of accumulated glycosaminoglycan was reduced in a dose dependent manner in both MPS VI skin fibroblasts and chondrocytes. Enzyme expression was maintained in skin fibroblasts for up to 41 days. Comparison of two promoters; the murine phosphoglycerate kinase gene promoter (pgk) and the myeloproliferative sarcoma virus long terminal repeat promoter (mpsv), demonstrated a higher level of marker gene expression driven by the mpsv promoter in both chondrocytes and synoviocytes in vitro. When injected into the rat knee, the expression of beta-galactosidase from the mpsv promoter was widespread across the synovial membrane and the fascia covering the cruciate ligaments and meniscus. No transduction of chondrocytes or ligament cells was observed. Transduction was maintained for at least 8 weeks after injection. These results indicate that the lentiviral vector can be used to deliver 4S to a range of joint tissues in vitro and efficiently transduce synovial cells and express beta-galactosidase in vivo.
Keywords: Joints
Cells, Cultured
Joint Diseases
Mucopolysaccharidosis VI
Transduction, Genetic
Genetic Vectors
Promoter Regions, Genetic
Genetic Therapy
Description: Copyright © 2009 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.ymgme.2009.02.008
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Appears in Collections:Aurora harvest 5
Paediatrics publications

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