en
Scientific article
Open access
English

ZAP-70 restoration in mice by in vivo thymic electroporation

Published inPloS one, vol. 3, no. 4, e2059
Publication date2008
Abstract

Viral and non-viral vectors have been developed for gene therapy, but their use is associated with unresolved problems of efficacy and safety. Efficient and safe methods of DNA delivery need to be found for medical application. Here we report a new monopolar system of non-viral electro-gene transfer into the thymus in vivo that consists of the local application of electrical pulses after the introduction of the DNA. We assessed the proof of concept of this approach by correcting ZAP-70 deficient severe combined immunodeficiency (SCID) in mice. The thymic electro-gene transfer of the pCMV-ZAP-70-IRES-EGFP vector in these mice resulted in rapid T cell differentiation in the thymus with mature lymphocytes detected by three weeks in secondary lymphoid organs. Moreover, this system resulted in the generation of long-term functional T lymphocytes. Peripheral reconstituted T cells displayed a diversified T cell receptor (TCR) repertoire, and were responsive to alloantigens in vivo. This process applied to the thymus could represent a simplified and effective alternative for gene therapy of T cell immunodeficiencies.

Keywords
  • Anesthesia
  • Animals
  • Cell Differentiation
  • Electric Conductivity
  • Electroporation/*methods
  • Green Fluorescent Proteins/metabolism
  • Immunophenotyping
  • Lymphoid Tissue/cytology
  • Mice
  • Receptors, Antigen, T-Cell/metabolism
  • Spleen/cytology
  • T-Lymphocytes/cytology
  • Thymus Gland/*cytology
  • Time Factors
  • Transfection
  • ZAP-70 Protein-Tyrosine Kinase/deficiency/*metabolism
Citation (ISO format)
IRLA, Magali et al. ZAP-70 restoration in mice by in vivo thymic electroporation. In: PloS one, 2008, vol. 3, n° 4, p. e2059. doi: 10.1371/journal.pone.0002059
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal1932-6203
547views
416downloads

Technical informations

Creation03/27/2012 8:59:01 AM
First validation03/27/2012 8:59:01 AM
Update time03/14/2023 5:19:48 PM
Status update03/14/2023 5:19:48 PM
Last indexation02/12/2024 11:15:58 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack