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Evaluation of macrophage-specific promoters using lentiviral delivery in mice.

Malin Levin ; Ulf Lidberg ; Pernilla Jirholt ; Martin Adiels (Institutionen för medicin, avdelningen för molekylär och klinisk medicin ; Institutionen för matematiska vetenskaper) ; Anna Wramstedt ; K Gustafsson ; D R Greaves ; S Li ; S Fazio ; M F Linton ; Sven-Olof Olofsson ; Jan Borén ; Inger Gjertsson
Gene therapy (1476-5462). Vol. 19 (2012), 11, p. 1041-7.
[Artikel, refereegranskad vetenskaplig]

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.



Denna post skapades 2013-03-26. Senast ändrad 2013-08-27.
CPL Pubid: 175033

 

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Institutioner (Chalmers)

Institutionen för medicin, avdelningen för molekylär och klinisk medicin (GU)
Wallenberglaboratoriet (GU)
Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning (GU)
Institutionen för matematiska vetenskaperInstitutionen för matematiska vetenskaper (GU)

Ämnesområden

Klinisk medicin

Chalmers infrastruktur