Efficacy of Gene Therapy for X-Linked Severe Combined Immunodeficiency

Hacein‐Bey‐Abina, Salima; Hauer, Julia; Lim, Annick; Pïcard, Capucine; Wang, Gary P.; Berry, Charles C.; Martinache, Chantal; Rieux-Laucat, Frédéric; Latour, Sylvain; Belohradsky, Bernd H.; Leiva, Lily E.; Sorensen, Ricardo U.; Debré, Marianne; Casanova, Jean‐Laurent; Blanche, Stéphane; Durandy, Anne; Bushman, Frederic D.; Fischer, Alain; Cavazzana, Marina

doi:10.1056/nejmoa1000164

Cited by 551 publications

(408 citation statements)

References 23 publications

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“…Human HSPC are commonly exploited for allogeneic and autologous transplantation, including GT as they have high differentiation and proliferation potential, long‐term survival capacity and self‐renewal ability 18, 21, 22, 24. They are phenotypically characterized by the absence of mature lineage markers (LIN‐) and by the expression of the CD34 molecule.…”

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Multiparametric Whole Blood Dissection: A one‐shot comprehensive picture of the human hematopoietic system

et al. 2017

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Human hematopoiesis is a complex and dynamic system where morphologically and functionally diverse mature cell types are generated and maintained throughout life by bone marrow (BM) Hematopoietic Stem/Progenitor Cells (HSPC). Congenital and acquired hematopoietic disorders are often diagnosed through the detection of aberrant frequency or composition of hematopoietic cell populations. We here describe a novel protocol, called “Whole Blood Dissection” (WBD), capable of analyzing in a single test‐tube, hematopoietic progenitors and all major mature cell lineages composing either BM or peripheral blood (PB) through a multiparametric flow‐cytometry analysis. WBD allows unambiguously identifying in the same tube up to 23 different blood cell types including HSPC subtypes and all the major myeloid and lymphoid lineage compartments at different stages of maturation, through a combination of 17 surface and 1 viability cell markers. We assessed the efficacy of WBD by analyzing BM and PB samples from adult (n = 8) and pediatric (n = 9) healthy donors highlighting age‐related shift in cell composition. We also tested the capability of WBD on detecting aberrant hematopoietic cell composition in clinical samples of patients with primary immunodeficiency or leukemia unveiling expected and novel hematopoietic unbalances. Overall, WBD allows unambiguously identifying >99% of the cell subpopulations composing a blood sample in a reproducible, standardized, cost‐, and time‐efficient manner. This tool has a wide range of potential pre‐clinical and clinical applications going from the characterization of hematopoietic disorders to the monitoring of hematopoietic reconstitution in patients after transplant or gene therapy. © 2017 The Authors. Cytometry Part A Published by Wiley Periodicals, Inc. on behalf of ISAC.

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Multiparametric Whole Blood Dissection: A one‐shot comprehensive picture of the human hematopoietic system

et al. 2017

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“…[3,4] To date, retroviral vectors have been used more than any other gene transfer vehicle for gene therapy of severe combined immunodeficiency (SCID) using the ex vivo approach. [1,[7][8][9] RNA viral vectors under development include oncoretroviruses encoding structural genes of gag, pol and env, and lentiviruses and spumaviruses, which contain additional viral proteins. [4,5] 2.1.1 Oncoretroviral Vectors-The first generation of retroviral vectors was developed from the murine leukaemia virus.…”

Section: Retroviral Vectorsmentioning

confidence: 99%

Advances in Gene Delivery Systems

et al. 2011

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The transfer of genes into cells, both in vitro and in vivo, is critical for studying gene function and conducting gene therapy. Methods that utilize viral and nonviral vectors, as well as physical approaches, have been explored. Viral vector-mediated gene transfer employs replication-deficient viruses such as retro-virus, adenovirus, adeno-associated virus and herpes simplex virus. A major advantage of viral vectors is their high gene delivery efficiency. The nonviral vectors developed so far include cationic liposomes, cationic polymers, synthetic peptides and naturally occurring compounds. These nonviral vectors appear to be highly effective in gene delivery to cultured cells in vitro but are significantly less effective in vivo. Physical methods utilize mechanical pressure, electric shock or hydrodynamic force to transiently permeate the cell membrane to transfer DNA into target cells. They are simpler than viral-and nonviral-based systems and highly effective for localized gene delivery. The past decade has seen significant efforts to establish the most desirable method for safe, effective and target-specific gene delivery, and good progress has been made. The objectives of this review are to (i) explain the rationale for the design of viral, nonviral and physical methods for gene delivery; (ii) provide a summary on recent advances in gene transfer technology; (iii) discuss advantages and disadvantages of each of the most commonly used gene delivery methods; and (iv) provide future perspectives.

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“…Previous reports have shown the occurrence of T-cell acute lymphoblastic leukaemia in four children treated with gene-transfer stem cells to correct their X-linked severe combined immunodeficiency. 13 However, in contrast to haematopoietic stem cells, retroviral vector integration to mature T-cells has been found to be a safe strategy as demonstrated by long-term engraftment of donor lymphocytes genetically engineered with the suicide gene thymidine kinase of herpes simplex virus after allogeneic stem cell transplantation. 14,15 Treatment with CART19 is an innovative immunotherapeutic approach to target leukaemic B-cells in patients with advanced chemotherapy-resistant CLL.…”

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A New Cellular Weapon to Kill Leukaemic B-Cells = سلاح خلوي جديد لقتل خلايا ( ب ) المسببة لإبيضاض الدم

Boulassel¹

2012

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Efficacy of Gene Therapy for X-Linked Severe Combined Immunodeficiency

Cited by 551 publications

References 23 publications

Multiparametric Whole Blood Dissection: A one‐shot comprehensive picture of the human hematopoietic system

Multiparametric Whole Blood Dissection: A one‐shot comprehensive picture of the human hematopoietic system

Advances in Gene Delivery Systems

A New Cellular Weapon to Kill Leukaemic B-Cells = سلاح خلوي جديد لقتل خلايا ( ب ) المسببة لإبيضاض الدم

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