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Open AccessJournal ArticleDOI

Challenges in vector and trial design using retroviral vectors for long-term gene correction in hematopoietic stem cell gene therapy.

Jacqueline Corrigan-Curay, +27 more
- 01 Jun 2012 - 
- Vol. 20, Iss: 6, pp 1084-1094
TLDR
Recent reports of insertional mutagenesis leading to myelodysplastic syndrome in a trial for chronic granulomatous disease and a case of leukemia in a Trial for Wiskott-Aldrich syndrome, both of which used g-retroviral vectors, underscored that this type of toxicity can also apply to other disease settings.
About: 
This article is published in Molecular Therapy.The article was published on 2012-06-01 and is currently open access. It has received 47 citations till now. The article focuses on the topics: Immunodeficiency & Severe combined immunodeficiency.

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Citations
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Journal ArticleDOI

Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome

Alessandro Aiuti, +39 more
- 23 Aug 2013 - 
TL;DR: A clinical protocol based on lentiviral vector (LV) gene transfer into autologous hematopoietic stem/progenitor cells (HSCs) resulted in robust, stable, and long-term engraftment of gene-corrected HSCs in the patients’ bone marrow, and the findings support the use of LV gene therapy to treat patients with WAS.
Journal ArticleDOI

Gene therapy on the move

Kerstin B. Kaufmann, +5 more
- 01 Nov 2013 - 
TL;DR: This review focuses on the application of gene therapy for the correction of inherited diseases, the limitations and drawbacks encountered in some of the early clinical trials and the revival of gene Therapy as a powerful treatment option for the Correction of monogenic disorders.
Journal ArticleDOI

Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy

Perry B. Hackett, +3 more
- 01 Apr 2013 - 
TL;DR: The Sleeping Beauty transposon/transposase system has been applied in clinical trials to stably insert a chimeric antigen receptor (CAR) to redirect T-cell specificity and the context in which the SB system can be harnessed for gene therapy and the human application of SB-modified CAR(+) T cells is described.
Journal ArticleDOI

Genome editing technologies: defining a path to clinic.

Jacqueline Corrigan-Curay, +18 more
- 01 May 2015 - 
TL;DR: Recently developed genomic editing technologies have the potential to be powerful tools for gene therapy because of their ability to inactivate genes, correct mutated sequences, or insert intact genes While the genomic editing field is advancing at an exceptionally rapid pace, there remain key issues regarding development of appropriate preclinical assays to evaluate off-target effects and establish safety.
Journal ArticleDOI

Preclinical Demonstration of Lentiviral Vector-mediated Correction of Immunological and Metabolic Abnormalities in Models of Adenosine Deaminase Deficiency

Denise A. Carbonaro, +20 more
- 01 Mar 2014 - 
TL;DR: In this article, a self-inactivating lentiviral vector (LV) with a codon-optimized human cADA gene under the control of the short form elongation factor-1α promoter (LV EFS ADA) was generated to improve the efficacy and safety of ADA-SCID gene therapy.
References
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Journal ArticleDOI

LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.

Salima Hacein-Bey-Abina, +35 more
- 17 Oct 2003 - 
TL;DR: Retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.
Journal ArticleDOI

What Makes Clinical Research Ethical

Ezekiel J. Emanuel, +2 more
- 24 May 2000 - 
TL;DR: 7 requirements are proposed that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies and are universal, although they must be adapted to the health, economic, cultural, and technological conditions in which clinical research is conducted.
Journal ArticleDOI

Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy

Nathalie Cartier, +26 more
- 06 Nov 2009 - 
TL;DR: Lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD, and progressive cerebral demyelination in the two patients stopped, a clinical outcome comparable to that achieved by allogeneic HCT.
Journal ArticleDOI

Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia

Marina Cavazzana-Calvo, +41 more
- 16 Sep 2010 - 
TL;DR: It is shown that, 33 months after lentiviral β-globin gene transfer, an adult patient with severe βE/β0-thalassaemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 21 months.
Journal ArticleDOI

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

Marion Ott, +26 more
- 01 Apr 2006 - 
TL;DR: The results suggest that gene therapy in combination with bone marrow conditioning can be successfully used to treat inherited diseases affecting the myeloid compartment such as CGD.
Related Papers (5)

Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease

Stefan Stein, +30 more
- 01 Feb 2010 - 

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

Marion Ott, +26 more
- 01 Apr 2006 - 

Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia

Marina Cavazzana-Calvo, +41 more
- 16 Sep 2010 - 

Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients

Steven J. Howe, +27 more
- 02 Sep 2008 - 

Gene Therapy for Immunodeficiency Due to Adenosine Deaminase Deficiency

Alessandro Aiuti, +30 more
- 10 Dec 2009 -