2020
DOI: 10.1016/j.jaci.2019.08.029
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Intrathymic adeno-associated virus gene transfer rapidly restores thymic function and long-term persistence of gene-corrected T cells

Abstract: Background: Patients with T-cell immunodeficiencies are generally treated with allogeneic hematopoietic stem cell transplantation, but alternatives are needed for patients without matched donors. An innovative intrathymic gene therapy approach that directly targets the thymus might improve outcomes. Objective: We sought to determine the efficacy of intrathymic adeno-associated virus (AAV) serotypes to transduce thymocyte subsets and correct the T-cell immunodeficiency in a zetaassociated protein of 70 kDa (ZAP… Show more

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Cited by 11 publications
(16 citation statements)
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References 148 publications
(189 reference statements)
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“…Furthermore, the medulla topology exhibits a highly convoluted shape, controlled by SP thymocytes. Tcra −/− and Zap70 −/− mice lacking SP thymocytes have a well-developed cortex but a severely reduced medulla [50,[78][79][80]. Similarly, Rag2 −/− mice showing an early block at the DN3 stage exhibit only ~20 small unconnected medullary islets [76].…”
Section: Ltα1β2/ltβr Axis Controls Medulla Organization and Central T...mentioning
confidence: 99%
“…Furthermore, the medulla topology exhibits a highly convoluted shape, controlled by SP thymocytes. Tcra −/− and Zap70 −/− mice lacking SP thymocytes have a well-developed cortex but a severely reduced medulla [50,[78][79][80]. Similarly, Rag2 −/− mice showing an early block at the DN3 stage exhibit only ~20 small unconnected medullary islets [76].…”
Section: Ltα1β2/ltβr Axis Controls Medulla Organization and Central T...mentioning
confidence: 99%
“…In the current issue, Pouzolles et al 9 used an alternative intrathymic ZAP-70 delivery based on adeno-associated virus (AAV) (Fig 1, C). In accordance with the higher efficacy of AAV compared with LV in transducing thymocytes, 8 intrathymic injection of AAV-ZAP-70 led to up to 5% of thymocyte transduction.…”
mentioning
confidence: 99%
“…In preclinical models of ZAP-70 immunodeficiency, LV encoding for ZAP-70 have been intrathymically injected. 8 In this issue, Pouzolles et al 9 injected AAV encoding for ZAP-70 in the thymi of ZAP-70-deficient mice. Ab, Antibody; BMT, bone marrow transplant.…”
mentioning
confidence: 99%
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“…The experience with XL-CGD and WAS continues to be immature but so far it has been shown partial correction of the disease [63][64][65][66]. Autologous gene-corrected T-cell therapy may resolve the defect in IEIs with restricted defects to the T cells, so far, this approach has been investigated in preclinical models [67][68][69][70][71][72].…”
Section: Gene Therapy For Primary Immunodeficienciesmentioning
confidence: 99%