In a new study appearing on August 1 in The Journal of Clinical Investigation, Naomi Taylor and colleagues from the Institut de Genetique Moleculaire de Montpellier provide the first report of a successful in vivo transcriptionally-targeted gene therapy for this genetic disease.
The researchers show that, in ZAP-70-deficient SCID mice, the ZAP-70 gene of interest can be directly introduced into T lymphoid progenitor cells by intrathymic injection of a T cell-specific lentiviral vector, avoiding any ex vivo manipulation that usually results in functional problems. This results in the presence of gene-modified T cells in the periphery. In their model, introduction of ZAP-70 corrected the defect in thymocyte maturation and T cells in the periphery were functional and polyclonal.
This work is the first demonstration of an in vivo therapy allowing specific genetic modulation of mature T lymphocytes. This has important implications, not only for the treatment of SCID but also for the treatment of other infectious and acquired diseases implicating T lymphocytes.
In a related commentary, Ruth Seggewiss and Cynthia Dunbar write, "using lentiviral vectors and in situ gene transfer may represent a safer approachavoiding factors potentially linked to leukemogenesis."
TITLE: In vivo correction of ZAP-70 immunodeficiency by intrathymic gene transfer
Institut de Genetique Moleculaire de Montpellier, Montpellier, France
Phone: 33-467-613-628; Fax: 33-467-040-231; E-mail: firstname.lastname@example.org
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