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Lentiviral Gene The...
Lentiviral Gene Therapy Using Cellular Promoters Cures Type 1 Gaucher Disease in Mice
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- Dahl, Maria (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Doyle, Alexander (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Olsson, Karin (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Månsson, Jan-Eric, 1946 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
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Marques, A. R. A. (author)
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Mirzaian, M. (author)
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Aerts, J. M. (author)
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- Ehinger, Mats (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Rothe, M. (author)
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Modlich, U. (author)
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Schambach, A. (author)
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- Karlsson, Stefan (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- English.
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In: Molecular Therapy. - : Elsevier BV. - 1525-0016 .- 1525-0024. ; 23:5, s. 835-844
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Abstract
Subject headings
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- Gaucher disease is caused by an inherited deficiency of the enzyme glucosylceramidase. Due to the lack of a fully functional enzyme, there is progressive build-up of the lipid component glucosylceramide. Insufficient glucosylceramidase activity results in hepatosplenomegaly, cytopenias, and bone disease in patients. Gene therapy represents a future therapeutic option for patients unresponsive to enzyme replacement therapy and lacking a suitable bone marrow donor. By proof-of-principle experiments, we have previously demonstrated a reversal of symptoms in a murine disease model of type 1 Gaucher disease, using gammaretroviral vectors harboring strong viral promoters to drive glucosidase beta-acid (GBA) gene expression. To investigate whether safer vectors can correct the enzyme deficiency, we utilized self-inactivating lentiviral vectors (SIN LVs) with the GBA gene under the control of human phosphoglycerate kinase (PGK) and CD68 promoter, respectively. Here, we report prevention of, as well as reversal of, manifest disease symptoms after lentiviral gene transfer. Glucosylceramidase activity above levels required for clearance of glucosylceramide from tissues resulted in reversal of splenomegaly, reduced Gaucher cell infiltration and a restoration of hematological parameters. These findings support the use of SIN-LVs with cellular promoters in future clinical gene therapy protocols for type 1 Gaucher disease.
Subject headings
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- CHRONIC GRANULOMATOUS-DISEASE
- BONE-MARROW TRANSPLANTATION
- ENZYME
- REPLACEMENT THERAPY
- IN-VIVO
- MOUSE MODEL
- HEMATOPOIETIC-CELLS
- RETROVIRAL VECTOR
- EXPRESSION
- CD68
- GLUCOCEREBROSIDASE
- Biotechnology & Applied Microbiology
- Genetics & Heredity
- Medicine
- Research & Experimental
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Dahl, Maria
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Doyle, Alexander
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Olsson, Karin
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Månsson, Jan-Eri ...
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Marques, A. R. A ...
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Mirzaian, M.
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show more...
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Aerts, J. M.
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Ehinger, Mats
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Rothe, M.
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Modlich, U.
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Schambach, A.
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Karlsson, Stefan
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Microbiology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Molecular Therap ...
- By the university
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University of Gothenburg
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Lund University