Lentiviral vectors transcriptionally targeted to hematopoietic cells by WASP gene proximal promoter sequences
Open Access
- 3 March 2005
- journal article
- research article
- Published by Springer Nature in Gene Therapy
- Vol. 12 (8) , 715-723
- https://doi.org/10.1038/sj.gt.3302457
Abstract
The development of vectors that express a therapeutic transgene efficiently and specifically in hematopoietic cells (HCs) is an important goal for gene therapy of hematological disorders. In order to achieve this, we used a 500 bp fragment from the proximal WASP gene promoter to drive the expression of the WASP cDNA in the context of a self-inactivating lentiviral vector. Single-round transduction of WASp-deficient herpesvirus saimiri (HVS)-immortalized cells as well as primary allospecific T cells from Wiskott–Aldrich syndrome (WAS) patients with this vector (WW) resulted in expression levels similar to those of control cells. Non-HCs were transduced with similar efficiency, but the levels of WASp were 135–350 times lower than those achieved in HCs. Additionally, transduction of WASp-deficient cells with WW conferred a selective growth advantage in vitro. Therefore, lentiviral vectors incorporating proximal promoter sequences from the WASP gene confer hematopoietic-specific, and physiological protein expression.Keywords
This publication has 34 references indexed in Scilit:
- Formation of human hepatocytes by human hematopoietic stem cells in sheepBlood, 2004
- Efficient lentiviral transduction of Herpesvirus saimiri immortalized T cells as a model for gene therapy in primary immunodeficienciesGene Therapy, 2004
- Differential contribution of Wiskott-Aldrich syndrome protein to selective advantage in T- and B-cell lineagesBlood, 2004
- LMO2 -Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1Science, 2003
- Specific transgene expression in human and mouse CD4+cells using lentiviral vectors with regulatory sequences from theCD4 geneBlood, 2003
- Functional correction of T cells derived from patients with the Wiskott–Aldrich syndrome (WAS) by transduction with an oncoretroviral vector encoding the WAS proteinGene Therapy, 2003
- Correction of ADA-SCID by Stem Cell Gene Therapy Combined with Nonmyeloablative ConditioningScience, 2002
- Hematopoiesis and stem cells: plasticity versus developmental heterogeneityNature Immunology, 2002
- Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem CellCell, 2001
- Identification of WASP mutations, mutation hotspots and genotype-phenotype disparities in 24 patients with the Wiskott-Aldrich syndromeHuman Genetics, 1996