Retroviral vectors related to the myeloproliferative sarcoma virus allow efficient expression in hematopoietic stem and precursor cell lines, but retroviral infection is reduced in more primitive cells.
Retroviral vectors are considered to be the most suited vehicles for somatic gene therapy with hematopoietic stem cells as targets. Retrovirus-mediated gene transfer into differentiation-restricted hematopoietic precursor (FDC-P1, FDC-P2) and multipotent progenitor (stem) cell lines (FDC-Pmix) is inefficient. Two cellular restrictions are involved. One is specific for stem but not precursor cells and is at the level of transcription. Due to a unique property of the transcriptional control region of the myeloproliferative sarcoma virus (MPSV), vectors derived from MPSV are not affected by this block. The second restriction occurs before proviral DNA synthesis and integration. This inhibition of effective viral infection depends on the state of differentiation, being more pronounced in multipotent clonogenic blast cells. This block to retroviral infection affects all retroviral vectors tested.
Beck-Engeser
G
G
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Federal Republic of Germany.
Stocking
C
C
Just
U
U
Albritton
L
L
Dexter
M
M
Spooncer
E
E
Ostertag
W
W
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics* / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000382:microbiology*; D051379:Mice; D008980:Moloney murine sarcoma virus / Q000235:genetics* / Q000502:physiology; D011533:Proviruses / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014170:Transformation, Genetic
D004279:DNA, Viral; D011991:Receptors, Virus