Orphan designation: Autologous CD34+ cells transfected with lentiviral vector containing the Wiskott-Aldrich syndrome protein gene, Treatment of Wiskott-Aldrich syndrome

2019 ◽  
Author(s):  
Keyword(s):  
Protein Gene ◽  
Lentiviral Vector ◽  
Orphan Designation ◽  
Wiskott Aldrich Syndrome ◽  
Gene Treatment ◽  
Cd34 Cells ◽  
Syndrome Protein

Evidence for Efficacy and Safety of Lentiviral Mediated Gene Transfer in T Cells and CD34+ Cells from Wiskott-Aldrich Syndrome Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3279-3279
Author(s):  
Samantha Scaramuzza ◽  
Sara Trifari ◽  
Francesco Marangoni ◽  
Silvana Martino ◽  
Ayse Metin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
Gene Transfer ◽  
Lentiviral Vector ◽  
Efficacy And Safety ◽  
Wiskott Aldrich Syndrome ◽  
Cd34 Cells ◽  
Was Gene

Abstract Wiskott-Aldrich Syndrome (WAS) is an X-linked primary immunodeficiency characterized by eczema, recurrent infections, severe hemorrhages and lymphomas. Transplantation of hematopoietic stem cells from HLA-identical sibling donors is a resolutive treatment, but it is available only for a minority of patients. Therapy based on the transplant of genetically correct autologous stem cells could represent a valid alternative approach. We investigated the efficacy and the safety of WAS gene transfer using HIV-based lentiviral vector encoding for WAS cDNA under the control of an autologous promoter (1.6 kb). T cells obtained from WAS patients showed normal level of WAS expression after lentiviral transduction. Transduced T cells showed a correction in TCR-driven proliferation and IL-2 production. Furthermore, a selective growth advantage of transduced T cells was observed in long-term in vitro cultures. Studies in T cell clones generated from transduced WAS CD4+ T cells revealed that 1–2 vector copies were necessary and sufficient to correct T cells function. CD34+ cells, isolated from mobilized peripheral blood and bone marrow of healthy donors, were transduced using WASP or GFP-encoding lentiviral vectors. Cells were cultured in the presence of different cytokines to investigate if WAS gene transfer could have any effect on short and long-term differentiation (CFU-C, LTC-IC and B/NK assays). Transduction resulted in a comparable number of CFU-C and LTC-IC colonies and normal B and NK cells differentiation with respect to untransduced cells. Furthermore, transduction of CD34+ cells isolated from the bone marrow of a WAS patient was performed under optimized culture conditions. Lentiviral gene transfer led to restoration of WASP expression in differentiated cells with copy number ranging from 1 to 5 copies per cell. In conclusion, our data demonstrate that the WAS promoter/cDNA-containing lentiviral vector can efficiently transduce and restore WASP expression in CD34+ cells and T cells from WAS patients. Experiments in the Rag2−/−/γchain- murine model are ongoing to test the efficacy and safety of the WASP transduced CD34+ cells. Together, our studies provide a preclinical basis for the implementation of a gene therapy trial for WAS patients.

Isolated X-linked thrombocytopenia in two unrelated families is associated with point mutations in the Wiskott-Aldrich syndrome protein gene

1996 ◽  
Vol 129 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Geneviève de Saint Basile ◽  
Rémi Dufourcq Lagelouse ◽  
Nathalie Lambert ◽  
Klaus Schwarz ◽  
Bernard Le Mareck ◽  
...  
Keyword(s):  
Protein Gene ◽  
Point Mutations ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

scholarly journals Whole Wiskott-Aldrich syndrome protein gene deletion identified by high throughput sequencing

2017 ◽  
Vol 16 (5) ◽  
pp. 6526-6531 ◽  
Author(s):  
Xiangling He ◽  
Runying Zou ◽  
Bing Zhang ◽  
Yalan You ◽  
Yang Yang ◽  
...  
Keyword(s):  
High Throughput ◽  
Gene Deletion ◽  
High Throughput Sequencing ◽  
Protein Gene ◽  
Wiskott Aldrich Syndrome ◽  
Syndrome Protein

scholarly journals A novel large deletion and single nucleotide insertion in the Wiskott-Aldrich syndrome protein gene

2014 ◽  
Vol 95 (1) ◽  
pp. 93-98
Author(s):  
Vera Gulácsy ◽  
Beáta Soltész ◽  
Carmen Petrescu ◽  
Mihaela Bataneant ◽  
Edit Gyimesi ◽  
...  
Keyword(s):  
Protein Gene ◽  
Large Deletion ◽  
Single Nucleotide ◽  
Wiskott Aldrich Syndrome ◽  
Nucleotide Insertion ◽  
Syndrome Protein

scholarly journals Preclinical Safety and Efficacy of Human CD34+ Cells Transduced With Lentiviral Vector for the Treatment of Wiskott-Aldrich Syndrome

2013 ◽  
Vol 21 (1) ◽  
pp. 175-184 ◽  
Author(s):  
Samantha Scaramuzza ◽  
Luca Biasco ◽  
Anna Ripamonti ◽  
Maria C Castiello ◽  
Mariana Loperfido ◽  
...  
Keyword(s):  
Lentiviral Vector ◽  
Safety And Efficacy ◽  
Wiskott Aldrich Syndrome ◽  
Human Cd34 ◽  
Cd34 Cells ◽  
Preclinical Safety
Sign in / Sign up

Export Citation Format

Share Document