Preclinical gene therapy studies of fanconi anemia with lentiviral vectors

A. Jacome; P. Río; S. Navarro; A. González; J.A. Casado; E. Almarza; M. Lamana; G. Guenechea; J.C. Segovia; J.A. Bueren

doi:10.1016/j.bcmd.2007.10.026

Preclinical gene therapy studies of fanconi anemia with lentiviral vectors

Blood Cells Molecules and Diseases ◽

10.1016/j.bcmd.2007.10.026 ◽

2008 ◽

Vol 40 (2) ◽

pp. 258

Author(s):

A. Jacome ◽

P. Río ◽

S. Navarro ◽

A. González ◽

J.A. Casado ◽

...

Keyword(s):

Gene Therapy ◽

Fanconi Anemia ◽

Lentiviral Vectors ◽

Therapy Studies

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Optimization of lentiviral vectors for the gene therapy of fanconi anemia

Blood Cells Molecules and Diseases ◽

10.1016/j.bcmd.2007.10.044 ◽

2008 ◽

Vol 40 (2) ◽

pp. 268

Author(s):

Africa Gonzalez-Murillo ◽

M. Luz Lozano ◽

Javier Molina-Estevez ◽

Elena Almarza ◽

Montserrat Aldea ◽

...

Keyword(s):

Gene Therapy ◽

Fanconi Anemia ◽

Lentiviral Vectors

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1211. Gene Therapy of Fanconi Anemia Groups A and C by Lentiviral Vectors Using Mouse as an Experimental Model: Comparison with Retroviral Vectors

Molecular Therapy ◽

10.1016/s1525-0016(16)44041-4 ◽

2002 ◽

Vol 5 (5) ◽

pp. S393-S394

Keyword(s):

Gene Therapy ◽

Experimental Model ◽

Fanconi Anemia ◽

Model Comparison ◽

Lentiviral Vectors ◽

Retroviral Vectors

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979. A Fanconi Anemia Gene Therapy Approach Based on the Transduction Hematopoietic Progenitors and Mesenchymal Stromal Cells with Lentiviral Vectors

Molecular Therapy ◽

10.1016/s1525-0016(16)39337-6 ◽

2009 ◽

Vol 17 ◽

pp. S373-S374

Keyword(s):

Gene Therapy ◽

Mesenchymal Stromal Cells ◽

Fanconi Anemia ◽

Stromal Cells ◽

Lentiviral Vectors ◽

Hematopoietic Progenitors ◽

Therapy Approach ◽

Gene Therapy Approach ◽

Fanconi Anemia Gene

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Development of Lentiviral Vectors with Optimized Transcriptional Activity for the Gene Therapy of Patients with Fanconi Anemia

Human Gene Therapy ◽

10.1089/hum.2009.141 ◽

2010 ◽

Vol 21 (5) ◽

pp. 623-630 ◽

Cited By ~ 32

Author(s):

África González-Murillo ◽

M. Luz Lozano ◽

Lara Álvarez ◽

Ariana Jacome ◽

Elena Almarza ◽

...

Keyword(s):

Gene Therapy ◽

Fanconi Anemia ◽

Transcriptional Activity ◽

Lentiviral Vectors

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Gene therapy of Fanconi anemia: preclinical efficacy using lentiviral vectors

Blood ◽

10.1182/blood-2002-04-1245 ◽

2002 ◽

Vol 100 (8) ◽

pp. 2732-2736 ◽

Cited By ~ 59

Author(s):

Francesco Galimi ◽

Meenakshi Noll ◽

Yoshiyuki Kanazawa ◽

Timothy Lax ◽

Cindy Chen ◽

...

Keyword(s):

Gene Therapy ◽

Bone Marrow ◽

Fanconi Anemia ◽

Bone Marrow Failure ◽

Allogeneic Bone Marrow Transplantation ◽

Lentiviral Vectors ◽

Myelogenous Leukemia ◽

Great Promise ◽

Allogeneic Bone ◽

Hematopoietic Progenitors

Fanconi anemia (FA) is an inherited cancer susceptibility syndrome caused by mutations in a DNA repair pathway including at least 6 genes(FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG). The clinical course of the disease is dominated by progressive, life-threatening bone marrow failure and high incidence of acute myelogenous leukemia and solid tumors. Allogeneic bone marrow transplantation (BMT) is a therapeutic option but requires HLA-matched donors. Gene therapy holds great promise for FA, but previous attempts to use retroviral vectors in humans have proven ineffective given the impaired proliferation potential of human FA hematopoietic progenitors (HPCs). In this work, we show that using lentiviral vectors efficient genetic correction can be achieved in quiescent hematopoietic progenitors from Fanca−/− andFancc−/−mice. Long-term repopulating HPCs were transduced by a single exposure of unfractionated bone marrow mononuclear cells to lentivectors carrying the normal gene. Notably, no cell purification or cytokine prestimulation was necessary. Resistance to DNA- damaging agents was fully restored by lentiviral transduction, allowing for in vivo selection of the corrected cells with nonablative doses of cyclophosphamide. This study strongly supports the use of lentiviral vectors for FA gene therapy in humans.

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