Comparison of three retroviral vector systems for transduction of nonobese diabetic/severe combined immunodeficiency mice repopulating human CD34+ cord blood cells

Cordula Leurs, Michael Jansen, Karen E. Pollok, Martin Heinkelein, Manfred Schmidt, Manuela Wissler, Dirk Lindemann, Christof Von Kalle, Axel Rethwilm, David A. Williams, Helmut Hanenberg

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

The use of recombinant vectors based on wild-type viruses that are absent in humans and are not associated with any disease in their natural animal hosts or in accidentally infected humans would add an additional level of safety for human somatic gene therapy approaches. These criteria are fulfilled by foamy viruses (FVs), a family of complex retroviruses whose members are widely found among mammals and are apathogenic in all hosts. Here, we show by comparison of identically designed vector constructs that recombinant retroviral vectors based on FVs were as efficient as lentiviral vectors in transducing nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice repopulating human CD34+ cord blood (CB) cells. The FV vector was able to achieve gene transfer levels up to 84% of engrafted human cells in a short overnight transduction protocol. In contrast, without prestimulation of the target cells, a human immunodeficiency virus type 1 (HIV-1)-based lentiviral vector pseudotyped with gibbon ape leukemia virus envelope (GALV Env) was nearly as inefficient as murine leukemia virus (MLV)-based oncoretroviral vectors in transducing NOD/SCID repopulating cells. The same HIV vector pseudotyped with the vesicular stomatitis virus glycoprotein G (VSV-G) achieved high marking efficiency. Clonality analysis of bone marrow samples showed oligoclonal hematopoiesis with single to multiple insertions per cell, both for FV and HIV vectors. These data demonstrate that vectors based on FVs warrant further investigation and development for medical use.

Original languageEnglish (US)
Pages (from-to)509-519
Number of pages11
JournalHuman gene therapy
Volume14
Issue number6
DOIs
StatePublished - Apr 10 2003

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Leurs, C., Jansen, M., Pollok, K. E., Heinkelein, M., Schmidt, M., Wissler, M., Lindemann, D., Von Kalle, C., Rethwilm, A., Williams, D. A., & Hanenberg, H. (2003). Comparison of three retroviral vector systems for transduction of nonobese diabetic/severe combined immunodeficiency mice repopulating human CD34+ cord blood cells. Human gene therapy, 14(6), 509-519. https://doi.org/10.1089/104303403764539305