Loss of retroviral gene expression in bone marrow reconstituted mice correlates with down-regulation of gene expression in long-term culture initiating cells.
The question of whether a retroviral vector is expressed in vivo after infection of hematopoietic stem cells remains unpredictable. In this study, we show that a switch off of retroviral sequences can be tested in vitro using the long-term bone marrow culture system. The time kinetics of the down-regulation of retroviral expression in vitro and in vivo have been demonstrated to be similar. The correlation of switch off events in both systems allows for evaluation of retroviral expression in vitro provided the silencing is caused by viral sequences. This approach could be useful for testing vectors for gene therapeutical applications of the hematopoietic system.
Lange
C
C
Max-Delbrück-Center of Molecular Medicine, Berlin, Germany.
Blankenstein
T
T
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D012190:Retroviridae / Q000235:genetics*; D013997:Time Factors; D014162:Transfection