Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors
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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: NAT BIOTECHNOL, Jahrgang 21, Nr. 9, 09.2003, S. 1040-6.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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
PY - 2003/9
Y1 - 2003/9
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.
KW - Amino Acid Sequence
KW - Capsid
KW - Cells, Cultured
KW - Coronary Vessels
KW - Dependovirus
KW - Endothelium, Vascular
KW - Gene Expression Regulation, Viral
KW - Gene Targeting
KW - Gene Transfer Techniques
KW - Genetic Therapy
KW - Genetic Vectors
KW - HeLa Cells
KW - Humans
KW - Molecular Sequence Data
KW - Peptide Library
KW - Sequence Analysis, Protein
KW - Transduction, Genetic
KW - Viral Proteins
KW - Comparative Study
KW - Evaluation Studies
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
KW - Research Support, U.S. Gov't, Non-P.H.S.
KW - Research Support, U.S. Gov't, P.H.S.
KW - Validation Studies
U2 - 10.1038/nbt856
DO - 10.1038/nbt856
M3 - SCORING: Journal article
C2 - 12897791
VL - 21
SP - 1040
EP - 1046
JO - NAT BIOTECHNOL
JF - NAT BIOTECHNOL
SN - 1087-0156
IS - 9
ER -