Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome
نویسندگان
چکیده
Alessandro Aiuti,* Luca Biasco, Samantha Scaramuzza, Francesca Ferrua, Maria Pia Cicalese, Cristina Baricordi, Francesca Dionisio, Andrea Calabria, Stefania Giannelli, Maria Carmina Castiello, Marita Bosticardo, Costanza Evangelio, Andrea Assanelli, Miriam Casiraghi, Sara Di Nunzio, Luciano Callegaro, Claudia Benati, Paolo Rizzardi, Danilo Pellin, Clelia Di Serio, Manfred Schmidt, Christof Von Kalle, Jason Gardner, Nalini Mehta, Victor Neduva, David J. Dow, Anne Galy, Roberto Miniero, Andrea Finocchi, Ayse Metin, Pinaki P. Banerjee, Jordan S. Orange, Stefania Galimberti, Maria Grazia Valsecchi, Alessandra Biffi , Eugenio Montini, Anna Villa, Fabio Ciceri, Maria Grazia Roncarolo, Luigi Naldini
منابع مشابه
Lentiviral hematopoietic stem cell gene therapy in patients with wiskott-Aldrich syndrome.
Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency caused by mutations in the gene encoding WASP, a protein regulating the cytoskeleton. Hematopoietic stem/progenitor cell (HSPC) transplants can be curative, but, when matched donors are unavailable, infusion of autologous HSPCs modified ex vivo by gene therapy is an alternative approach. We used a lentiviral vector encoding functio...
متن کاملGeneration of a lentiviral vector producer cell clone for human Wiskott-Aldrich syndrome gene therapy
We have developed a producer cell line that generates lentiviral vector particles of high titer. The vector encodes the Wiskott-Aldrich syndrome (WAS) protein. An insulator element has been added to the long terminal repeats of the integrated vector to limit proto-oncogene activation. The vector provides high-level, stable expression of WAS protein in transduced murine and human hematopoietic c...
متن کاملDevelopment of lentiviral gene therapy for Wiskott Aldrich syndrome.
BACKGROUND Wiskott Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency. This complex disease is characterised by microthrombocytopenia, recurrent infections, eczema and is associated with a high incidence of autoimmunity and of lymphoid malignancies. WAS is attracting growing attention not only because it highlights the rich cellular and systems biology revolving around cytoskele...
متن کاملPreclinical Safety and Efficacy of Human CD34+ Cells Transduced With Lentiviral Vector for the Treatment of Wiskott-Aldrich Syndrome
Gene therapy with ex vivo-transduced hematopoietic stem/progenitor cells may represent a valid therapeutic option for monogenic immunohematological disorders such as Wiskott-Aldrich syndrome (WAS), a primary immunodeficiency associated with thrombocytopenia. We evaluated the preclinical safety and efficacy of human CD34+ cells transduced with lentiviral vectors (LV) encoding WAS protein (WASp)....
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Wiskott-Aldrich syndrome (WAS) is a life-threatening immunodeficiency caused by mutations within the WAS gene. Viral gene therapy to restore WAS protein (WASp) expression in hematopoietic cells of patients with WAS has the potential to improve outcomes relative to the current standard of care, allogeneic bone marrow transplantation. However, the development of viral vectors that are both safe a...
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Gene therapy with hematopoietic stem cells (HSC) is an attractive therapeutic strategy for several forms of primary immunodeficiencies. Current approaches are based on ex vivo gene transfer of the therapeutic gene into autologous HSC by vector-mediated gene transfer. In the past decade, substantial progress has been achieved in the treatment of severe combined immundeficiencies (SCID)-X1, adeno...
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