Research Article

Development of an adenoviral vector system with adenovirus serotype 35 tropism; efficient transient gene transfer into primary malignant hematopoietic cells

  1. Marcus Nilsson1,
  2. Johan Ljungberg1,
  3. Johan Richter1,
  4. Thomas Kiefer1,3,
  5. Mattias Magnusson1,
  6. André Lieber4,
  7. Bengt Widegren2,
  8. Stefan Karlsson1,
  9. Xiaolong Fan1,2,*

Article first published online: 10 MAR 2004

DOI: 10.1002/jgm.543

Issue

The Journal of Gene Medicine

The Journal of Gene Medicine

Volume 6, Issue 6, pages 631–641, June 2004

Additional Information

How to Cite

Nilsson, M., Ljungberg, J., Richter, J., Kiefer, T., Magnusson, M., Lieber, A., Widegren, B., Karlsson, S. and Fan, X. (2004), Development of an adenoviral vector system with adenovirus serotype 35 tropism; efficient transient gene transfer into primary malignant hematopoietic cells. J. Gene Med., 6: 631–641. doi: 10.1002/jgm.543

Author Information

  1. 1

    Department of Molecular Medicine and Gene Therapy, Lund University, SE-22184 Lund, Sweden

  2. 2

    Department of Immunology, Lund University, SE-22184 Lund, Sweden

  3. 3

    Department of Hematology and Oncology, University of Greifswald, D-17489 Greifswald, Germany

  4. 4

    Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington 98195, USA

*Department of Molecular Medicine and Gene Therapy, Lund University, BMC A12, 221 84 Lund, Sweden.

Publication History

  1. Issue published online: 25 MAY 2004
  2. Article first published online: 10 MAR 2004
  3. Manuscript Accepted: 9 DEC 2003
  4. Manuscript Revised: 3 DEC 2003
  5. Manuscript Received: 26 AUG 2003

Funded by

  • Swedish Cancer Society, the Royal Physiografic Society in Lund, the Crafoord Foundation, the Erik Philip-Sörensen Foundation, the Gunnar Nilsson Cancer Foundation, the Georg Danielsson Foundation, the Funds of Lund University Hospital, the Hedvig Foundation, and the Swedish Gene Therapy Program

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Keywords:

  • leukemia;
  • chronic myeloid leukemia;
  • chronic lymphocytic leukemia;
  • gene transfer;
  • adenoviral vector;
  • fiber retargeting

Abstract

Background

A paucity of coxsackie adenovirus receptor (CAR) hampers the adenovirus serotype 5 (Ad5)-based vector-mediated gene transfer into malignant hematopoietic cells. Fiber-retargeted adenoviral vectors with species B tropism can potentially bypass the CAR requirement and facilitate efficient gene transfer into malignant hematopoietic cells.

Methods

For feasible generation of fiber-retargeted adenoviral vectors, we have modified the versatile AdEasy system with a chimeric fiber gene encoding the Ad5 fiber tail domain and Ad35 fiber shaft and knob domains. An Ad5-based vector encoding the green fluorescent protein (GFP) gene under the control of the PGK promoter with Ad35 fiber receptor specificity was generated (Ad5F35-GFP). The Ad5F35-GFP vector-mediated gene transfer efficiency was compared with a fiber non-modified Ad5-GFP vector, which also encodes the GFP gene under the control of the PGK promoter.

Results

We demonstrated that a variety of Ad5-refractory malignant myeloid and B lymphoid cell lines were highly permissive to the Ad5F35-GFP vector infection. Importantly, primary chronic myeloid leukemic (CML) cells and chronic lymphocytic leukemia (CLL) B cells were superiorly transduced by the Ad5F35-GFP vector at a multiplicity of infection (MOI) of 100 compared with the Ad5-GFP vector.

Conclusions

Our study will facilitate the generation of fiber-retargeted adenoviral vectors and enable transient genetic manipulation of primary malignant hematopoietic cells. Copyright © 2004 John Wiley & Sons, Ltd.

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