Lentiviral hematopoietic stem cell gene therapy in patients with wiskott-aldrich syndrome

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 SerioManfred 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

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622 Citations (Scopus)


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 functional WASP to genetically correct HSPCs from three WAS patients and reinfused the cells after a reduced-intensity conditioning regimen. All three patients showed stable engraftment of WASP-expressing cells and improvements in platelet counts, immune functions, and clinical scores. Vector integration analyses revealed highly polyclonal and multilineage haematopoiesis resulting from the gene-corrected HSPCs. Lentiviral gene therapy did not induce selection of integrations near oncogenes, and no aberrant clonal expansion was observed after 20 to 32 months. Although extended clinical observation is required to establish long-term safety, lentiviral gene therapy represents a promising treatment for WAS.

Original languageEnglish
Article number1233151
Issue number6148
Publication statusPublished - 2013
Externally publishedYes


ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Aiuti, A., Biasco, L., Scaramuzza, S., Ferrua, F., Cicalese, M. P., Baricordi, C., Dionisio, F., Calabria, A., Giannelli, S., Castiello, M. C., Bosticardo, M., Evangelio, C., Assanelli, A., Casiraghi, M., Di Nunzio, S., Callegaro, L., Benati, C., Rizzardi, P., Pellin, D., ... Naldini, L. (2013). Lentiviral hematopoietic stem cell gene therapy in patients with wiskott-aldrich syndrome. Science, 341(6148), [1233151]. https://doi.org/10.1126/science.1233151