Foamy viral vector integration sites in SCID-repopulating cells after MGMTP140K-mediated in vivo selection.

Abstract

Foamy virus (FV) vectors are promising for hematopoietic stem cell (HSC) gene therapy but preclinical data on the clonal composition of FV vector-transduced human repopulating cells is needed. Human CD34(+) human cord blood cells were transduced with an FV vector encoding a methylguanine methyltransferase (MGMT)P140K transgene, transplanted into immunodeficient NOD/SCID IL2Rγ(null) mice, and selected in vivo for gene-modified cells. The retroviral insertion site profile of repopulating clones was examined using modified genomic sequencing PCR. We observed polyclonal repopulation with no evidence of clonal dominance even with the use of a strong internal spleen focus forming virus promoter known to be genotoxic. Our data supports the use of FV vectors with MGMTP140K for HSC gene therapy but also suggests additional safety features should be developed and evaluated.

DOI: 10.1038/gt.2015.20

Cite this paper

@article{Olszko2015FoamyVV, title={Foamy viral vector integration sites in SCID-repopulating cells after MGMTP140K-mediated in vivo selection.}, author={Miles E. Olszko and Jennifer Adair and Ian van der Linde and Dustin T. Rae and Patricia Trobridge and Jonah Hocum and David J Rawlings and H-P Kiem and Grant Trobridge}, journal={Gene therapy}, year={2015}, volume={22 7}, pages={591-5} }