Evaluation of macrophage-specific promoters using lentiviral delivery in mice

M. C. Levin, U. Lidberg, P. Jirholt, M. Adiels, A. Wramstedt, K. Gustafsson, D. R. Greaves, S. Li, S. Fazio, M. F. Linton, S. O. Olofsson, J. Borén, I. Gjertsson

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

In gene therapy, tissue-specific promoters are useful tools to direct transgene expression and improve efficiency and safety. Macrophage-specific promoters (MSPs) have previously been published using different delivery systems. In this study, we evaluated five different MSPs fused with green fluorescent protein (GFP) to delineate the one with highest specificity using lentiviral delivery. We compared three variants of the CD68 promoter (full length, the 343-bp proximal part and the 150-bp proximal part) and two variants (in forward and reverse orientation) of a previously characterized synthetic promoter derived from elements of transcription factor genes. We transduced a number of cell lines and primary cells in vitro. In addition, hematopoietic stem cells were transduced with MSPs and transferred into lethally irradiated recipient mice. Fluorescence activated cell sorting analysis was performed to determine the GFP expression in different cell populations both in vitro and in vivo. We showed that MSPs can efficiently be used for lentiviral gene delivery and that the 150-bp proximal part of the CD68 promoter provides primarily macrophage-specific expression of GFP. We propose that this is the best currently available MSP to use for directing transgene expression to macrophage populations in vivo using lentiviral vectors.

Original languageEnglish (US)
Pages (from-to)1041-1047
Number of pages7
JournalGene Therapy
Volume19
Issue number11
DOIs
StatePublished - Nov 2012

Keywords

  • Lentivirus
  • Macrophage
  • Promoter

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Levin, M. C., Lidberg, U., Jirholt, P., Adiels, M., Wramstedt, A., Gustafsson, K., Greaves, D. R., Li, S., Fazio, S., Linton, M. F., Olofsson, S. O., Borén, J., & Gjertsson, I. (2012). Evaluation of macrophage-specific promoters using lentiviral delivery in mice. Gene Therapy, 19(11), 1041-1047. https://doi.org/10.1038/gt.2011.195