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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. Retroviral vectors must have a high efficiency of infection and sufficient transcriptional expression to be used in somatic gene therapy protocols. Beck-Engeser et al., show here that differentiation-specific cellular parameters determine the expression and infection efficiency of retroviral vectors in multipotent hematopoietic precursor cell lines. Vectors related to the myeloproliferative sarcoma virus (MPSV) permit expression in all hematopoietic cells, but infection efficiency is still reduced.
Beck‐Engeser et al. (Mon,) studied this question.