Generation of high-titer retroviral vector-producing macrophages as vehicles for in vivo gene transfer

Gene Therapy
S PastorinoM C Bosco

Abstract

The goal of this project was to develop a novel gene transfer system based on macrophages (Mphi) as shuttles of recombinant retroviral vectors carrying therapeutic or marker genes. The murine Mphi cell line WGL5 was used as a source of Mphi for this study. We generated retrovirus-producing Mphi by transducing the WGL5 cells with a replication-defective retroviral vector carrying the enhanced green fluorescent protein (EGFP) reporter gene and the Moloney murine leukemia virus (MoMLV) as helper virus. We demonstrated stable integration of the recombinant retrovirus in the Mphi genome, efficient recombinant retrovirus production, and EGFP gene delivery to different cell lines in vitro. To evaluate Mphi-mediated EGFP gene transfer in vivo, allogeneic mice were injected s.c. with the retrovirus-producing WGL5 Mphi, that gave rise to solid tumor masses at the injection site, highly infiltrated with host leukocytes. We observed EGFP fluorescence in tumor-infiltrating CD4(+) and CD8(+) host T lymphocytes, providing direct evidence of the ability of engineered Mphi to mediate EGFP gene delivery to host cells in vivo. Moreover, we showed that retrovirus-producing Mphi could home to different organs in vivo following i.v. injection into m...Continue Reading

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Citations

May 17, 2013·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Ho Won LeeJaetae Lee
Dec 2, 2004·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Larisa Pereboeva, David T Curiel
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Oct 26, 2006·Journal of Leukocyte Biology·Maura PuppoLuigi Varesio
Mar 27, 2019·Therapeutic Delivery·Steen J Madsen, Henry Hirschberg
Sep 18, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Ji Hyoung SeoJaetae Lee

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