High Levels of Transgene Expression Following Transduction of Long‐Term NOD/SCID‐Repopulating Human Cells with a Modified Lentiviral Vector

Abstract

ABSTRACT

Evaluation of Tet-on system to avoid transgene down-regulation in ex vivo gene transfer to the CNS

“…Transgene down-regulation was evident in most cells of LV-Tet clones at day 10. Since LV vectors direct sustained in vivo transgene expression in the rat brain, 10,27 and LV vector-mediated gene transfer in other cell transplantation paradigms can sustain gene expression in vivo, for instance hematopoietic stem cells 28 or islet grafts, 29 the observed transgene silencing in HiB5 ex vivo gene transfer to the CNS suggests that the responsible mechanisms for transgene down-regulation are not directly related to the transcriptional unit. More likely, down-regulation is a consequence of the grafted HiB5 cells switching from a proliferative state to a differentiated state in which the gene expression profile is changed and the overall transcriptional activity is reduced.…”

Comparative studies on cellular gene regulation by HIV-1 based vectors: implications for quality control of vector production

“…4 As an alternative vector system, lentiviral vectors based on HIV-1 has been under significant development. The corrections in primate models of Parkinson's disease 5 and the high efficiency of stem cell gene transfer by HIV-1-based lentiviral vectors, 6 and the first clinical trial using lentiviral vectors demonstrate a promising future for their clinical applications. There have been no direct reports on insertional mutagenesis by lentiviral vectors; however, the severe pathogenic nature of their parental virus (HIV-1) is still a major safety concern surrounding these vectors and prevents the progress with their clinical application.…”

Glioma tropism of lentivirally transduced hematopoietic progenitor cells

“…Lentivirally GFP-transduced human cord blood CD34 + HPC have previously been transplanted into NOD/SCID mice to examine gene transfer and expression in engrafting human cells. Fifteen weeks post-transplantation, 37±12% of engrafted human cells expressed GFP introduced by a lentivirus (35). For our further studies, we selected the syngeneic SMA-560-VM/Dk model.…”