Evaluation of macrophage-specific promoters using lentiviral delivery in mice.
Artikel i vetenskaplig tidskrift, 2012

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.

Författare

Malin Levin

Göteborgs universitet

Ulf Lidberg

Göteborgs universitet

Pernilla Jirholt

Göteborgs universitet

Martin Adiels

Chalmers, Matematiska vetenskaper

Göteborgs universitet

Anna Wramstedt

Göteborgs universitet

K Gustafsson

D R Greaves

S Li

S Fazio

M F Linton

Sven-Olof Olofsson

Göteborgs universitet

Jan Borén

Göteborgs universitet

Inger Gjertsson

Göteborgs universitet

Gene Therapy

0969-7128 (ISSN) 1476-5462 (eISSN)

Vol. 19 11 1041-7

Ämneskategorier

Klinisk medicin

DOI

10.1038/gt.2011.195

PubMed

22130447