29 research outputs found
Increased Mortality in Metal-on-Metal versus Non-Metal-on-Metal Primary Total Hip Arthroplasty at 10 Years and Longer Follow-Up: A Systematic Review and Meta-Analysis
Analysis and Stochastic
Targeted gene correction of human hematopoietic stem cells for the treatment of Wiskott - Aldrich Syndrome
Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency with severe platelet abnormalities and complex immunodeficiency. Although clinical gene therapy approaches using lentiviral vectors have produced encouraging results, full immune and platelet reconstitution is not always achieved. Here we show that a CRISPR/Cas9-based genome editing strategy allows the precise correction of WAS mutations in up to 60% of human hematopoietic stem and progenitor cells (HSPCs), without impairing cell viability and differentiation potential. Delivery of the editing reagents to WAS HSPCs led to full rescue of WASp expression and correction of functional defects in myeloid and lymphoid cells. Primary and secondary transplantation of corrected WAS HSPCs into immunodeficient mice showed persistence of edited cells for up to 26 weeks and efficient targeting of long-term repopulating stem cells. Finally, no major genotoxicity was associated with the gene editing process, paving the way for an alternative, yet highly efficient and safe therapy
Targeted gene correction of human hematopoietic stem cells for the treatment of Wiskott - Aldrich Syndrome
Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency with severe
platelet abnormalities and complex immunodeficiency. Although clinical gene therapy
approaches using lentiviral vectors have produced encouraging results, full immune and
platelet reconstitution is not always achieved. Here we show that a CRISPR/Cas9-based
genome editing strategy allows the precise correction of WAS mutations in up to 60% of
human hematopoietic stem and progenitor cells (HSPCs), without impairing cell viability and
differentiation potential. Delivery of the editing reagents to WAS HSPCs led to full rescue of
WASp expression and correction of functional defects in myeloid and lymphoid cells. Primary
and secondary transplantation of corrected WAS HSPCs into immunodeficient mice showed
persistence of edited cells for up to 26 weeks and efficient targeting of long-term repopulating
stem cells. Finally, no major genotoxicity was associated with the gene editing process,
paving the way for an alternative, yet highly efficient and safe therapy