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Modulation of Moloney Leukemia Virus Long Terminal Repeat Transcriptional Activity by the Murine CD4 Silencer in Retroviral Vectors

Authors
Journal
Virology
0042-6822
Publisher
Elsevier
Publication Date
Volume
276
Issue
1
Identifiers
DOI: 10.1006/viro.2000.0519
Keywords
  • Cd4
  • Silencer
  • Retroviral Vectors
  • Lymphocytes
  • Gene Therapy
Disciplines
  • Biology

Abstract

Abstract We investigated whether CD4 gene regulatory sequences might be useful for developing transcriptionally targeted Moloney murine leukemia virus (Mo-MLV)-based retroviral vectors for gene expression specifically in CD4 + cells. We could modulate Mo-MLV long terminal repeat (LTR) activity by inserting a 438-bp-long fragment containing the murine CD4 silencer in the LTR of the vector; both β-galactosidase and green fluorescent protein reporter gene activities were strongly down-regulated in both murine and human CD8 + cells, but not in CD4 + lymphoid cell lines and freshly isolated lymphocytes transduced with this vector, compared with the findings using a control vector carrying wild-type LTRs. Titration experiments on NIH-3T3 cells revealed that inclusion of the CD4 silencer in the LTRs did not reduce the titer of the vectors. These findings indicate that a cellular silencer can be successfully included in retroviral vectors, where it maintains its transcription-regulatory function, thus suggesting a novel approach to transcriptional targeting.

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