Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors

Oliver J. Müller, Felix Kaul, Matthew D. Weitzman, Renata Pasqualini, Wadih Arap, Jürgen A. Kleinschmidt, Martin Trepel

Research output: Contribution to journalArticle

246 Citations (Scopus)

Abstract

Characterizing the molecular diversity of the cell surface is critical for targeting gene therapy. Cell type-specific binding ligands can be used to target gene therapy vectors. However, targeting systems in which optimum eukaryotic vectors can be selected on the cells of interest are not available. Here, we introduce and validate a random adeno-associated virus (AAV) peptide library in which each virus particle displays a random peptide at the capsid surface. This library was generated in a three-step system that ensures encoding of displayed peptides by the packaged DNA. As proof-of-concept, we screened AAV-libraries on human coronary artery endothelial cells. We observed selection of particular peptide motifs. The selected peptides enhanced transduction in coronary endothelial cells but not in control nonendothelial cells. This vector targeting strategy has advantages over other combinatorial approaches such as phage display because selection occurs within the context of the capsid and may have a broad range of applications in biotechnology and medicine.

Original languageEnglish (US)
Pages (from-to)1040-1046
Number of pages7
JournalNature biotechnology
Volume21
Issue number9
DOIs
StatePublished - Sep 1 2003

Fingerprint

Peptide Library
Gene therapy
Dependovirus
Viruses
Genetic Therapy
Peptides
Capsid
Endothelial cells
Libraries
Endothelial Cells
Bacteriophages
Biotechnology
Virion
Medicine
Coronary Vessels
Ligands
DNA

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

Cite this

Müller, O. J., Kaul, F., Weitzman, M. D., Pasqualini, R., Arap, W., Kleinschmidt, J. A., & Trepel, M. (2003). Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors. Nature biotechnology, 21(9), 1040-1046. https://doi.org/10.1038/nbt856

Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors. / Müller, Oliver J.; Kaul, Felix; Weitzman, Matthew D.; Pasqualini, Renata; Arap, Wadih; Kleinschmidt, Jürgen A.; Trepel, Martin.

In: Nature biotechnology, Vol. 21, No. 9, 01.09.2003, p. 1040-1046.

Research output: Contribution to journalArticle

Müller, OJ, Kaul, F, Weitzman, MD, Pasqualini, R, Arap, W, Kleinschmidt, JA & Trepel, M 2003, 'Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors', Nature biotechnology, vol. 21, no. 9, pp. 1040-1046. https://doi.org/10.1038/nbt856
Müller OJ, Kaul F, Weitzman MD, Pasqualini R, Arap W, Kleinschmidt JA et al. Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors. Nature biotechnology. 2003 Sep 1;21(9):1040-1046. https://doi.org/10.1038/nbt856
Müller, Oliver J. ; Kaul, Felix ; Weitzman, Matthew D. ; Pasqualini, Renata ; Arap, Wadih ; Kleinschmidt, Jürgen A. ; Trepel, Martin. / Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors. In: Nature biotechnology. 2003 ; Vol. 21, No. 9. pp. 1040-1046.
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