Fibronectin fragment CH-296 inhibits apoptosis and enhances ex vivo gene transfer by murine retrovirus and human lentivirus vectors independent of viral tropism in nonhuman primate CD34+ cells.
The fibronectin fragment CH-296 improved gene transfer to cytokine-mobilized nonhuman primate CD34+ cells irrespective of tropism to the MoMLV, GaLV, and VSV-G envelope proteins using murine stem cell virus (MSCV) and human immunodeficiency virus-1 (HIV-1)-based retrovirus vectors. For the HIV-1 lentivirus vector, CH-296 enhanced gene transfer in the absence of added hematopoietic growth factors necessary for ex vivo stem cell expansion. In the presence of CH-296, apoptosis of CD34+ cells was inhibited, and in mobilized peripheral blood CD34+ cells, cell division was stimulated as measured by cell history/tracking experiments.
Donahue
R E
RE
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 21892, USA.
Sorrentino
B P
BP
Hawley
R G
RG
An
D S
DS
Chen
I S
IS
Wersto
R P
RP
D000818:Animals; D018952:Antigens, CD34; D017209:Apoptosis; D002460:Cell Line; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D017988:Gammaretrovirus / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta; D008979:Moloney murine leukemia virus / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D018523:Tropism; D014759:Viral Envelope Proteins / Q000235:genetics; D014779:Virus Replication
D018952:Antigens, CD34; D005353:Fibronectins; D010446:Peptide Fragments; D014759:Viral Envelope Proteins