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Lentiviral Vectors ...
Lentiviral Vectors with Cellular Promoters Correct Anemia and Lethal Bone Marrow Failure in a Mouse Model for Diamond-Blackfan Anemia
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- Debnath, Shubhranshu (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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- Jaako, Pekka (author)
- Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine
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- Siva, Kavitha (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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- Rothe, Michael (author)
- Hannover Medical School
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- Chen, Jun (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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- 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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- Gaspar, H. Bobby (author)
- University College London
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- Flygare, Johan (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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- Schambach, Axel (author)
- Harvard University,Boston Children's Hospital,Hannover Medical School
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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, 2017
- 2017
- English.
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In: Molecular Therapy. - : Elsevier BV. - 1525-0016. ; 25:8, s. 1805-1814
- Related links:
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Abstract
Subject headings
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- Diamond-Blackfan anemia is a congenital erythroid hypoplasia and is associated with physical malformations and a predisposition to cancer. Twenty-five percent of patients with Diamond-Blackfan anemia have mutations in a gene encoding ribosomal protein S19 (RPS19). Through overexpression of RPS19 using a lentiviral vector with the spleen focus-forming virus promoter, we demonstrated that the Diamond-Blackfan anemia phenotype can be successfully treated in Rps19-deficient mice. In our present study, we assessed the efficacy of a clinically relevant promoter, the human elongation factor 1α short promoter, with or without the locus control region of the β-globin gene for treatment of RPS19-deficient Diamond-Blackfan anemia. The findings demonstrate that these vectors rescue the proliferation defect and improve erythroid development of transduced RPS19-deficient bone marrow cells. Remarkably, bone marrow failure and severe anemia in Rps19-deficient mice was cured with enforced expression of RPS19 driven by the elongation factor 1α short promoter. We also demonstrate that RPS19-deficient bone marrow cells can be transduced and these cells have the capacity to repopulate bone marrow in long-term reconstituted mice. Our results collectively demonstrate the feasibility to cure RPS19-deficient Diamond-Blackfan anemia using lentiviral vectors with cellular promoters that possess a reduced risk of insertional mutagenesis. Diamond-Blackfan anemia is a congenital erythroid hypoplasia. Twenty-five percent of patients have mutations in a gene encoding ribosomal protein S19. Using an RPS19-deficient mouse model, Debnath et al. demonstrate the feasibility to cure RPS19-deficient Diamond-Blackfan anemia by means of lentiviral vectors with cellular promoters that possess a reduced risk of insertional mutagenesis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- Diamond-Blackfan anemia
- Gene therapy
- Lentiviral vectors
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Debnath, Shubhra ...
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Jaako, Pekka
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Siva, Kavitha
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Rothe, Michael
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Chen, Jun
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Dahl, Maria
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show more...
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Gaspar, H. Bobby
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Flygare, Johan
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Schambach, Axel
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Karlsson, Stefan
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show less...
- About the subject
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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 Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Molecular Therap ...
- By the university
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Lund University