About: Stability and expression of human MDR1 in retroviral vectors for gene therapy.     Goto   Sponge   NotDistinct   Permalink

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  • The human multidrug resistance 1 (hMDR1) gene encodes a membrane-located protein (P-gp), which is capable to pump xenobiotics out of cells. This property makes hMDR1 potentially useful for gene therapy, since its overexpression can protect genetically modified hematopoietic cells against the effects of cytotoxic agents. However, ectopic expression of hMDR1 mRNA from retroviral vectors is compromised by an aberrant splicing which results in a production of a non-functional protein. Here we report that 1) our construct (QQ-SA) improved the functional properties of MDR1 compared with the wild type, although the aberrant splicing was not fully eliminated. 2) The other mutations tested resulted in the elimination of the aberrant splicing, however, they had a negative impact on the P-gp function. 3) The use of human packaging cells GP2-293 greatly reduced the frequency of MDR1 aberrant splicing in retroviral vectors and seems to be a valuable tool for generating retroviruses containing MDR1 cDNA.
  • The human multidrug resistance 1 (hMDR1) gene encodes a membrane-located protein (P-gp), which is capable to pump xenobiotics out of cells. This property makes hMDR1 potentially useful for gene therapy, since its overexpression can protect genetically modified hematopoietic cells against the effects of cytotoxic agents. However, ectopic expression of hMDR1 mRNA from retroviral vectors is compromised by an aberrant splicing which results in a production of a non-functional protein. Here we report that 1) our construct (QQ-SA) improved the functional properties of MDR1 compared with the wild type, although the aberrant splicing was not fully eliminated. 2) The other mutations tested resulted in the elimination of the aberrant splicing, however, they had a negative impact on the P-gp function. 3) The use of human packaging cells GP2-293 greatly reduced the frequency of MDR1 aberrant splicing in retroviral vectors and seems to be a valuable tool for generating retroviruses containing MDR1 cDNA. (en)
Title
  • Stability and expression of human MDR1 in retroviral vectors for gene therapy.
  • Stability and expression of human MDR1 in retroviral vectors for gene therapy. (en)
skos:prefLabel
  • Stability and expression of human MDR1 in retroviral vectors for gene therapy.
  • Stability and expression of human MDR1 in retroviral vectors for gene therapy. (en)
skos:notation
  • RIV/00023736:_____/02:00000098!RIV/2003/MZ0/L33003/N
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  • O/17
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  • P(NE6689)
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  • 664792
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  • RIV/00023736:_____/02:00000098
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  • P-gp; hMDR1; aberrant splicing; retroviral vector; gene therapy (en)
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  • [0D27A962CB89]
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  • Praha
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  • Praha
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  • XIII. český a slovenský hematologický a transfuziologický kongres s mezinárodní účastí.
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  • Fuchs, Ota
  • Jelínek, J.
  • Čmejla, Radek
  • Čmejlová, Jana
  • Žáková, Dana
  • Baum, C.
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  • Agentura Carolina
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