Lentivirus Vector Mediated Hematopoietic Stem Cell Gene Transfer of Common Gamma-Chain Cytokine Receptor in Rhesus Macaques
The bulletin of the Yamaguchi Medical School Volume 51 Issue 3-4
Page 37-40
published_at 2004-12
Title
Lentivirus Vector Mediated Hematopoietic Stem Cell Gene Transfer of Common Gamma-Chain Cytokine Receptor in Rhesus Macaques
Creators
Dong Sung An.
Source Identifiers
We examined the efficiency of marking, gene expression, and transplant of bone marrow and peripheral blood CD34 +cells using a lentivirus vector in non-human primate model systems. In vitrocytokine stimulation was not required to achieve efficient transduction of CD34 +cells resulting in marking and gene expression of the reporter gene encoding enhanced green fluorescent protein (EGFP) following transplant of the CD34 +cells. Monkeys transplanted with mobilized peripheral blood CD34 +cells resulted in EGFP expression in 1 to 10% of multilineage peripheral blood cells, including red blood cells and platelets, stable for 5 years to date. The relative level of gene expression utilizing a lentiviral vector bearing a RhMLV promoter is 2- to 10-fold greater than that utilizing a lenntivirus vector bearing the cytomegalovirus immediate-early promoter. In contrast, in animals transplanted with autologous bone mallow CD34 +cells, multilineage EGFP expression was evident initially but diminished over time. We further tested our lentivirus vector system by demonstrating gene transfer of the human common gamma-chain cytokine receptor gene (νc), deficient in X-linked SCID patients and recently successfully used to treat disease. Marking was 0.42 and 0.001 HIV-1 vector DNA copy per 100 cells in two animals. To date, all EGFP- and νc-transplanted animals are healthy. This system may prove useful for expression of therapeutic genes in human hematopoientic cells.
Languages
eng
Resource Type
departmental bulletin paper
Publishers
Yamaguchi University Graduate School of Medicine
Date Issued
2004-12
File Version
Version of Record
Access Rights
open access
Relations
[ISSN]0513-1812
[NCID]AA00594272
Schools
医学部