High-level expression of hemoglobin A in human thalassemic erythroid progenitor cells following lentiviral vector delivery of an antisense snRNA (Articolo in rivista)

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Label
  • High-level expression of hemoglobin A in human thalassemic erythroid progenitor cells following lentiviral vector delivery of an antisense snRNA (Articolo in rivista) (literal)
Anno
  • 2003-01-01T00:00:00+01:00 (literal)
Alternative label
  • Vacek MM, Ma H, Gemignani F, Lacerra G, Kafri T, Kole R. (2003)
    High-level expression of hemoglobin A in human thalassemic erythroid progenitor cells following lentiviral vector delivery of an antisense snRNA
    in Blood
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Vacek MM, Ma H, Gemignani F, Lacerra G, Kafri T, Kole R. (literal)
Pagina inizio
  • 104 (literal)
Pagina fine
  • 111 (literal)
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  • 101 (literal)
Rivista
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  • In questo lavoro si dimostra che virus lentovirali con snRNA modificato (U7.623), contenente una sequenza antisenso a regione di siti di splicing anomali che causano inattivazione del gene beta globinico, trasfettati in cellule HeLa che esprimono mutanti talassemici e soprattutto in cellule staminali ematopoietiche da pazienti con difetti di splicing a carico dei geni beta globinici, corregge il difetto talassemico portando ad un aumentato livello del mRNA beta globinico correttamente processato e alla sintesi della proteina. (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1 University of North Caroline,Chapell Hill, USA; 2 IARC, Lyon, France; 3 Istituto di Genetica e Biofisica - CNR, Italy. (literal)
Titolo
  • High-level expression of hemoglobin A in human thalassemic erythroid progenitor cells following lentiviral vector delivery of an antisense snRNA (literal)
Abstract
  • Mutations at nucleotides 654, 705, or 745 in intron 2 of the human beta-globin gene activate aberrant 3' and 5' splice sites within the intron and prevent correct splicing of beta-globin pre-mRNA, resulting in inhibition of beta-globin synthesis and in consequence beta-thalassemia. Transfection of HeLa cells expressing the 3 thalassemic mutants with modified U7 snRNA (U7.623), containing a sequence antisense to a region between the aberrant splice sites, reduced the incorrect splicing of pre-mRNA and led to increased levels of the correctly spliced beta-globin mRNA and protein. A lentiviral vector carrying the U7.623 gene was effective in restoration of correct splicing in the model cell lines for at least 6 months. Importantly, the therapeutic value of this system was demonstrated in hematopoietic stem cells and erythroid progenitor cells from a patient with IVS2-745/IVS2-1 thalassemia. Twelve days after transduction of the patient cells with the U7.623 lentiviral vector, the levels of correctly spliced beta-globin mRNA and hemoglobin A were approximately 25-fold over background. These results should be regarded as a proof of principle for lentiviral vector-based gene therapy for beta-thalassemia. (literal)
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