کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9989639 1580761 2005 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Bicistronic lentiviral vector corrects β-hexosaminidase deficiency in transduced and cross-corrected human Sandhoff fibroblasts
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Bicistronic lentiviral vector corrects β-hexosaminidase deficiency in transduced and cross-corrected human Sandhoff fibroblasts
چکیده انگلیسی
Sandhoff disease is an autosomal recessive neurodegenerative disease characterized by a GM2 ganglioside intralysosomal accumulation. It is due to mutations in the β-hexosaminidases β-chain gene, resulting in a β-hexosaminidases A (αβ) and B (ββ) deficiency. Mono and bicistronic lentiviral vectors containing the HEXA or/and HEXB cDNAs were constructed and tested on human Sandhoff fibroblasts. The bicistronic SIV.ASB vector enabled a massive restoration of β-hexosaminidases activity on synthetic substrates and a 20% correction on the GM2 natural substrate. Metabolic labeling experiments showed a large reduction of ganglioside accumulation in SIV.ASB transduced cells, demonstrating a correct recombinant enzyme targeting to the lysosomes. Moreover, enzymes secreted by transduced Sandhoff fibroblasts were endocytosed in deficient cells via the mannose 6-phosphate pathway, allowing GM2 metabolism restoration in cross-corrected cells. Therefore, our bicistronic lentivector supplying both α- and β-subunits of β-hexosaminidases may provide a potential therapeutic tool for the treatment of Sandhoff disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 20, Issue 2, November 2005, Pages 583-593
نویسندگان
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