We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Foamy viral vector integration sites in SCID-repopulating cells after MGMTP140K-mediated in vivo selection.
- Authors
Olszko, M E; Adair, J E; Linde, I; Rae, D T; Trobridge, P; Hocum, J D; Rawlings, D J; Kiem, H-P; Trobridge, G D
- 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 IL2Rγnull 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.
- Subjects
FOAMY viruses; GENE therapy; HEMATOPOIETIC stem cells; METHYLTRANSFERASES; POLYMERASE chain reaction; BLOOD cells
- Publication
Gene Therapy, 2015, Vol 22, Issue 7, p591
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/gt.2015.20