Improved transduction of human sheep repopulating cells by retrovirus vectors pseudotyped with feline leukemia virus type C or RD114 envelopes
Open Access
- 1 July 2005
- journal article
- Published by American Society of Hematology in Blood
- Vol. 106 (1) , 51-58
- https://doi.org/10.1182/blood-2004-11-4491
Abstract
Gene therapy for hematopoietic diseases has been hampered by the low frequency of transduction of human hematopoietic stem cells (HSCs) with retroviral vectors pseudotyped with amphotropic envelopes. We hypothesized that transduction could be increased by the use of retroviral vectors pseudotyped with envelopes that recognize more abundant cellular receptors. The levels of mRNA encoding the receptors of the feline retroviruses, RD114 and feline leukemia virus type C (FeLV-C), were significantly higher than the level of gibbon ape leukemia virus (GaLV) receptor mRNA in cells enriched for human HSCs (Lin– CD34+ CD38–). We cotransduced human peripheral blood CD34+ cells with equivalent numbers of FeLV-C and GALV or RD114 and GALV-pseudotyped retroviruses for injection into fetal sheep. Analysis of DNA from peripheral blood and bone marrow from recipient sheep demonstrated that FeLV-C– or RD114-pseudotyped vectors were present at significantly higher levels than GALV-pseudotyped vectors. Analysis of individual myeloid colonies demonstrated that retrovirus vectors with FeLV-C and RD114 pseudotypes were present at 1.5 to 1.6 copies per cell and were preferentially integrated near known genes We conclude that the more efficient transduction of human HSCs with either FeLV-C– or RD114-pseudotyped retroviral particles may improve gene transfer in human clinical trials.Keywords
This publication has 68 references indexed in Scilit:
- Identification of a Human Heme Exporter that Is Essential for ErythropoiesisCell, 2004
- LMO2 -Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1Science, 2003
- Concentrated RD114-pseudotyped MFGS-gp91phox vector achieves high levels of functional correction of the chronic granulomatous disease oxidase defect in NOD/SCID/ 2-microglobulin-/- repopulating mobilized human peripheral blood CD34+ cellsBlood, 2003
- A Serious Adverse Event after Successful Gene Therapy for X-Linked Severe Combined ImmunodeficiencyNew England Journal of Medicine, 2003
- Lentiviral vectors pseudotyped with a modified RD114 envelope glycoprotein show increased stability in sera and augmented transduction of primary lymphocytes and CD34+ cells derived from human and nonhuman primatesBlood, 2002
- Optimization of Gene Transfer into Primitive Human Hematopoietic Cells of Granulocyte-Colony Stimulating Factor–Mobilized Peripheral Blood Using Low-Dose Cytokines and Comparison of a Gibbon Ape Leukemia Virus Versus an RD114-Pseudotyped Retroviral VectorHuman Gene Therapy, 2002
- Pharmacologically regulated in vivo selection in a large animalBlood, 2002
- Optimization of Retroviral Gene Transduction of Mobilized Primitive Hematopoietic Progenitors by Using Thrombopoietin, Flt3, and Kit Ligands and RetroNectin CultureHuman Gene Therapy, 1999
- Retroviral Transfer of the Glucocerebrosidase Gene into CD34+ Cells from Patients with Gaucher Disease: In Vivo Detection of Transduced Cells without MyeloablationHuman Gene Therapy, 1998
- IL2RGbase: a database of γc-chain defects causing human X-SCIDImmunology Today, 1996