Abstract
Tay-Sachs disease is a severe neurodegenerative disorder due to mutations in the HEXA gene coding for the α-chain of the α-β heterodimeric lysosomal enzyme β-hexosaminidase A (HexA). Because no treatment is available for this disease, we have investigated the possibility of enzymatic correction of HexA-deficient cells by HEXA gene transfer. Human HEXA cDNA was subcloned into a retroviral plasmid generating to G.HEXA vector. The best Ψ-CRIP producer clone of G.HEXA retroviral particles was isolated, and murine HexA-deficient fibroblasts derived from hexa -/- mice were transduced with the G.HEXA vector. Transduced cells overexpressed the α-chain, resulting in the synthesis of interspecific HexA (human α-chain/murine β-chain) and in a total correction of HexA deficiency. The α-chain was secreted in the culture medium and taken up by HexA-deficient cells via mannose-6-phosphate receptor binding, allowing for the restoration of intracellular HexA activity in non-transduced cells.
Original language | English (US) |
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Pages (from-to) | 831-838 |
Number of pages | 8 |
Journal | Human molecular genetics |
Volume | 7 |
Issue number | 5 |
DOIs | |
State | Published - May 1998 |
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Genetics(clinical)