Development of safety vector for the gene therapy of ribosomal protein S19 deficient Diamond-Blackfan anemia
| Project/Area Number |
15591025
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | National Institute of Infectious Diseases (2004)
Keio University (2003) |
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Principal Investigator |
HAMAGUCHI Isao National Institute of Infectious Diseases, Department of Safety Research on Blood and Biological Products, Chief, 血液・安全性研究部, 室長 (90348780)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Diamond-Blackfan anemia / RPS19 / hematopoietic stem cells / knockout mouse / siRNA / Red cell production / Diamond-Blackfan anemia / レンチウイルスベクター / ハイブリッドベクター |
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| Research Abstract |
We have developed new lentiviral vector for the gene therapy of ribosomal protein S19(RPS19) deficient Diamond-Blackfan anemia(DBA). Since the strong transgene expression activity was required for this vector, we developed hybrid vector between lentiviral backborn and retrovirus U3 region in the LTR(long term repeat). Using this vector high transduction efficiency was observed in the DBA patient hematopoietic stem cells (Mol.Ther., 2003).
In order to analyze the mechanisms for abnormal differentiation of erythroid leneage cells in DBA, RPS19-knock out mice were generated in the corraboration study with Niklas Dahl. In this mice we could not detect the typical phenotype of anemia correlated to human disease. It is suggested that the function of mouse RPS19 is different from human RPS19 (Mol.Cell.Biol., 2004).
For further analyze of human RPS19 function, we developed lentiviral vector containing siRNA-expression cassette against RPS19. When we transduced siRNA gene against RPS19 in human cord blood CD34+ cells, the growth and differentiation of erythroid leneage cells were disturbed in the transduced cells (Blood, 2005).
Together with these results, we have revealed the function of RPS19 and developed the stem cell model for DBA using siRNA vector. By using this model we would like to analyze the whole mechanisms of DBA, and develop the new therapy.
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Report
(3 results)
Research Products
(8 results)
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[Journal Article] Deficiency of Ribosomal Protein S19 in CD34+ cells generated by siRNA blocks erythroid development and mimics defects seen in Diamond-Blackfan anemia.2005
Author(s)
Flygare J, Kiefer T, Miyake K, Utsugisawa T, Hamaguchi I, Da Costa L, Richter J, Davey EJ, Matsson H, Dahl N, Wiznerowicz M, Torono D, Karlsson S
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Journal Title
Blood 105
Pages: 4627-4634
Description
「研究成果報告書概要(欧文)」より
Related Report
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