TY - JOUR
T1 - Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors
AU - Müller, Oliver J.
AU - Kaul, Felix
AU - Weitzman, Matthew D.
AU - Pasqualini, Renata
AU - Arap, Wadih
AU - Kleinschmidt, Jürgen A.
AU - Trepel, Martin
N1 - Funding Information:
We thank Hugo A. Katus, Florian Otto, Roland Mertelsmann, Christoph Peters, Christoph Leder and Mirta Grifman for helpful discussions and critical reading of the manuscript, Marie Follo and Andreas Hunziker for DNA sequencing, Lothar Pilz for statistical analyses, Elisete de Lima-Hahn, Katrin Schlenker, Kristin Schmidt and Petra Poberschin for technical assistance. This work was supported by the US Department of Defense Grant DAMD 17-01-1-0003 to M.T. M.T. was also supported in part by the Susan G. Komen Breast Cancer Foundation, O.M. is supported by the Deutsche Forschungsgemeinschaft (MU 1654/2-1) and R.P. is supported by the National Cancer Institute (CA 99106). The 293T cells were used with kind permission of David Baltimore, and the Kasumi cells were a gift from Michael Lübbert. We thank the Laboratoire de Thérapie Génique, Nantes, France, for providing wild-type Ad5, and Jude Samulski for the pSub201, pXX2 and pXX6 plasmids.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nbt856
DO - 10.1038/nbt856
M3 - Article
C2 - 12897791
AN - SCOPUS:0042360384
SN - 1087-0156
VL - 21
SP - 1040
EP - 1046
JO - Nature biotechnology
JF - Nature biotechnology
IS - 9
ER -