Tracking of specific integrant clones in dogs treated with foamy virus vectors.
Vector integration can lead to proto-oncogene activation and malignancies during hematopoietic stem cell gene therapy. We previously used foamy virus vectors to deliver the CD18 gene under the control of an internal murine stem cell virus promoter and successfully treated dogs with canine leukocyte adhesion deficiency. Here we have tracked the copy numbers of 11 specific proviruses found in these animals for 36-42 months after transplantation, including examples within or near proto-oncogenes, tumor suppressor genes, and genes unrelated to cancer. We found no evidence for clonal expansion of any of the clones, including those with proviruses in the MECOM gene (MDS1-EVI1 complex). These results suggest that although foamy virus vectors may integrate near proto-oncogenes, this does not necessarily lead to clonal expansion and malignancies. Additionally, we show that copy number estimates of these specific proviruses based on linker-mediated PCR results are different from those obtained by quantitative PCR, but can provide a qualitative assessment of provirus levels.
Ohmine
Ken
K
Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Li
Yi
Y
Bauer
Thomas R
TR
Hickstein
Dennis D
DD
Russell
David W
DW
D000818:Animals; D002999:Clone Cells; D004285:Dogs; D015316:Genetic Therapy; D005822:Genetic Vectors; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000821:virology*; D011519:Proto-Oncogenes; D011533:Proviruses / Q000235:genetics; D016092:Spumavirus / Q000235:genetics*; D016662:Virus Integration