Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1

@article{Ott2006CorrectionOX,
  title={Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1},
  author={Marion Gabriele Ott and Manfred Schmidt and Kerstin Schwarzwaelder and Stefan Stein and Ulrich Siler and Ulrike Koehl and Hanno Glimm and Klaus K{\"u}hlcke and Andrea J Schilz and Hana Kunkel and Sonja Naundorf and Andrea Brinkmann and Annette Deichmann and Marlene Fischer and Claudia R. Ball and Ingo H. Pilz and Cynthia E. Dunbar and Yang Du and Nancy A. Jenkins and Neal G. Copeland and Ursula Lüthi and Moustapha Hassan and Adrian James Thrasher and Dieter Hoelzer and Christof von Kalle and Reinhard A. Seger and Manuel Grez},
  journal={Nature Medicine},
  year={2006},
  volume={12},
  pages={401-409}
}
Gene transfer into hematopoietic stem cells has been used successfully for correcting lymphoid but not myeloid immunodeficiencies. Here we report on two adults who received gene therapy after nonmyeloablative bone marrow conditioning for the treatment of X-linked chronic granulomatous disease (X-CGD), a primary immunodeficiency caused by a defect in the oxidative antimicrobial activity of phagocytes resulting from mutations in gp91phox. We detected substantial gene transfer in both individuals… Expand

Paper Mentions

Interventional Clinical Trial
This is a phase II exploratory study conducted to evaluate the safety and efficacy of the combination of Ibuprofen, G-CSF and Plerixafor as stem cell mobilization regimen in patients… Expand
ConditionsChronic Granulomatous Disease X-linked (X-CGD)
InterventionDrug
Interventional Clinical Trial
The aim of the study is to evaluate the side effects and risks after infusion of retroviral gene corrected autologous CD34+ cells of the peripheral blood of chemotherapy conditioned… Expand
ConditionsChronic Granulomatous Disease
InterventionGenetic
Interventional Clinical Trial
The aim of the study is to evaluate the side effects and risks after infusion of retroviral gene corrected autologous CD34+ cells of the peripheral blood of chemotherapy conditioned… Expand
ConditionsGranulomatous Disease, Chronic
InterventionDrug
TALEN-mediated functional correction of X-linked chronic granulomatous disease in patient-derived induced pluripotent stem cells.
TLDR
It is demonstrated that TALEN-mediated integration of a myelo-specific gp91phox transgene into AAVS1 of patient-derived iPSCs represents a safe and efficient way to generate autologous, functionally corrected granulocytes. Expand
Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease
TLDR
It is shown that forced overexpression of EVI1 in human cells disrupts normal centrosome duplication, linking EVI 1 activation to the development of genomic instability, monosomy 7 and clonal progression toward myelodysplasia. Expand
Hematopoietic Tumors in a Mouse Model of X-linked Chronic Granulomatous Disease after Lentiviral Vector-Mediated Gene Therapy.
TLDR
The data support the long-term efficacy of LV-mediated HSPC GT in X CGD mice and provide a safety warning because the chronic inflammatory XCGD background may contribute to oncogenesis. Expand
MDS1/EVI1 and PRDM16 deregulation in hematopoiesis after experimental and clinical gene transfer
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  • Biology
  • 2012
TLDR
This first ever large scale IDLV integration analyses yielded more than 800 unique, mappable IDLV ISs in vitro, and provided direct molecular evidence that the background integration of D64V mutant IDLVs is not mediated by residual catalytic activity of the mutant integrase. Expand
Lentiviral gene therapy for X-linked chronic granulomatous disease
TLDR
Nine severely affected X-linked CGD patients who received ex vivo autologous CD34 + hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning received early evidence supporting its safety and efficacy in treating patients with X- linked chronic granulomatous disease. Expand
Recent Advances in Gene Therapy and Modeling of Chronic Granulomatous Disease.
TLDR
This review focuses on the application of gene therapy for the CGD, the limitations encountered in current clinical trials, advantages and disadvantages of endonucleases in gene correction and modeling with CRISPR/Cas9 approach. Expand
Advances in the treatment of Chronic Granulomatous Disease by gene therapy.
TLDR
These studies demonstrated the safety and limitations of gene transfer into hematopoietic stem cells of CGD patients using retroviral vectors and allowed partial correction of the granulocytic function with a significant clinical benefit in treated patients. Expand
Gene therapy for chronic granulomatous disease.
TLDR
It is concluded that gene therapy salvage treatment for severe infection unresponsive to conventional therapy can provide life-saving clinical benefit to CGD patients lacking a suitable donor. Expand
Retroviral gene therapy for X-linked chronic granulomatous disease: results from phase I/II trial.
  • H. Kang, C. Bartholomae, +12 authors H. Ahn
  • Biology, Medicine
  • Molecular therapy : the journal of the American Society of Gene Therapy
  • 2011
TLDR
Overall, the gene transfer procedure did not produce any serious adverse effects and was able to convert a significant fraction of blood cells to biologically functional cells, albeit for a short period of time. Expand
Retroviral vector integration in post-transplant hematopoiesis in mice conditioned with either submyeloablative or ablative irradiation
TLDR
Findings support the concept that vector integration can confer a selection bias, and suggest that the intensity of the conditioning regimen may further influence the effects of vector integration on clonal selection in post-transplant engraftment and hematopoiesis. Expand
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