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Mol Ther Methods Clin Dev. 2014 Apr 09;1:14010. doi: 10.1038/mtm.2014.10. eCollection 2014.

Lentiviral vectors containing mouse Csf1r control elements direct macrophage-restricted expression in multiple species of birds and mammals.

Molecular therapy. Methods & clinical development

Clare Pridans, Simon Lillico, Bruce Whitelaw, David A Hume

Affiliations

  1. The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Scotland , UK.

PMID: 26015955 PMCID: PMC4362345 DOI: 10.1038/mtm.2014.10

Abstract

The development of macrophages requires signaling through the lineage-restricted receptor Csf1r. Macrophage-restricted expression of transgenic reporters based upon Csf1r requires the highly conserved Fms-intronic regulatory element (FIRE). We have created a lentiviral construct containing mouse FIRE and promoter. The lentivirus is capable of directing macrophage-restricted reporter gene expression in mouse, rat, human, pig, cow, sheep, and even chicken. Rat bone marrow cells transduced with the lentivirus were capable of differentiating into macrophages expressing the reporter gene in vitro. Macrophage-restricted expression may be desirable for immunization or immune response modulation, and for gene therapy for lysosomal storage diseases and some immunodeficiencies. The small size of the Csf1r transcription control elements will allow the insertion of large "cargo" for applications in gene therapy and vaccine delivery.

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