> Kreppel, Ulm - Kochanek, Ulm <

Abstract I Investigator I Publications

Cytokine-mediated targeting of adenovirus gene transfer vectors for efficient gene delivery to hematopoietic cells

Adenovirus gene transfer vectors based on the human serotype 5 are attractive vectors for gene transfer. They can be produced to high titers and transduce a wide variety of different cells including quiescent cells. However, they largely fail to transduce hematopoietic stem and progenitor cells. This can be attributed to the lack of the coxsackie and adenovirus receptor CAR and the lack of ?v integrins on the surface of these cells. The overall goals of this project are (i) to define strategies for efficient virus vector-mediated gene delivery into CD34+ hematopoietic progenitor cells based on the use of cytokines as ligands, and (ii) to provide a detailed side-by-side comparison of the clonogenic potential of CD34+ hematopoietic progenitor cells after transduction with non-targeted and targeted firstgeneration and HC-Ad vectors. The results are likely to impact the development of rationally designed targeted gene transfer vectors based on different viruses and also non-viral vectors.

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Florian Kreppel, Dr. rer. nat.
University of Ulm
Division of Gene Therapy
Helmholtzstraße 8/1
89081 Ulm
e-mail: florian.kreppel[at]uni-ulm.de
www.uni-ulm.de/gentherapie

Stefan Kochanek, Prof. Dr. med.
University of Ulm
Division of Gene Therapy
Helmholtzstraße 8/1
89081 Ulm
e-mail: stefan.kochanek[at]uni-ulm.de
www.uni-ulm.de/gentherapie

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5 selected Publications related to the project

Espenlaub S, Corjon S, Engler T, Fella C, Ogris M, Wagner E, Kochanek S, Kreppel F. Capsomere-specific fluorescent labeling of adenovirus vector particles allows for detailed analysis of intracellular particle trafficking and of the performance of bioresponsive bonds for vector capsid modifications [Internet]. Hum Gene Ther 2010 Apr; Available from: www.ncbi.nlm.nih.gov/pubmed/20384482

Espenlaub S, Wortmann A, Engler T, Corjon S, Kochanek S, Kreppel F. Reductive amination as a strategy to reduce adenovirus vector promiscuity by chemical capsid modification with large polysaccharides. J Gene Med 2008 Dec;10(12):1303-1314.

Corjon S, Wortmann A, Engler T, van Rooijen N, Kochanek S, Kreppel F. Targeting of adenovirus vectors to the LRP receptor family with the high-affinity ligand RAP via combined genetic and chemical modification of the pIX capsomere. Mol. Ther 2008 Nov;16(11):1813-1824.

Kreppel F, Kochanek S. Modification of adenovirus gene transfer vectors with synthetic polymers: a scientific review and technical guide. Mol. Ther 2008 Jan;16(1):16-29.

Wortmann A, Vöhringer S, Engler T, Corjon S, Schirmbeck R, Reimann J, Kochanek S, Kreppel F. Fully detargeted polyethylene glycol-coated adenovirus vectors are potent genetic vaccines and escape from pre-existing anti-adenovirus antibodies. Mol. Ther 2008 Jan;16(1):154-162.

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