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.
journal_name
Gene Therjournal_title
Gene therapyauthors
Olszko ME,Adair JE,Linde I,Rae DT,Trobridge P,Hocum JD,Rawlings DJ,Kiem HP,Trobridge GDdoi
10.1038/gt.2015.20subject
Has Abstractpub_date
2015-07-01 00:00:00pages
591-5issue
7eissn
0969-7128issn
1476-5462pii
gt201520journal_volume
22pub_type
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