Pre-arrayed Pan-AAV Peptide Display Libraries for Rapid Single-Round Screening
Abstract
Display of short peptides on the surface of adeno-associated viruses (AAVs) is a powerful technology for the generation of gene therapy vectors with altered cell specificities and/or transduction efficiencies. Following its extensive prior use in the best characterized AAV serotype 2 (AAV2), recent reports also indicate the potential of other AAV isolates as scaffolds for peptide display. In this study, we systematically explored the respective capacities of 13 different AAV capsid variants to tolerate 27 peptides inserted on the surface followed by production of reporter-encoding vectors. Single-round screening in pre-arrayed 96-well plates permitted rapid and simple identification of superior vectors in >90 cell types, including T cells and primary cells. Notably, vector performance depended not only on the combination of capsid, peptide, and cell type, but also on the position of the inserted peptide and the nature of flanking residues. For optimal data availability and accessibility, all results were assembled in a searchable online database offering multiple output styles. Finally, we established a reverse-transduction pipeline based on vector pre-spotting in 96- or 384-well plates that facilitates high-throughput library panning. Our comprehensive illustration of the vast potential of alternative AAV capsids for peptide display should accelerate their in vivo screening and application as unique gene therapy vectors.
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BibTeX
@article{borner2026prearrayed,
title = {{Pre-arrayed Pan-AAV Peptide Display Libraries for Rapid Single-Round Screening}},
author = {Kathleen Börner and Eike Kienle and Lin-Ya Huang and Jonas Weinmann and Anna Sacher and Philipp Bayer and Christian Stüllein and Julia Fakhiri and Laura Zimmermann and Adrian Westhaus and Jürgen Beneke and Nina Beil and Ellen Wiedtke and Carolin Schmelas and Dominik Miltner and Alexander Rau and Holger Erfle and Hans-Georg Kräusslich and Martin Müller and Mavis Agbandje-Mckenna and Dirk Grimm},
journal = {Molecular Therapy},
year = {2026},
month = sep,
doi = {10.1016/j.ymthe.2020.02.009},
url = {https://hal.science/hal-05771967v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Pre-arrayed Pan-AAV Peptide Display Libraries for Rapid Single-Round Screening
AU - Kathleen Börner
AU - Eike Kienle
AU - Lin-Ya Huang
AU - Jonas Weinmann
AU - Anna Sacher
AU - Philipp Bayer
AU - Christian Stüllein
AU - Julia Fakhiri
AU - Laura Zimmermann
AU - Adrian Westhaus
AU - Jürgen Beneke
AU - Nina Beil
AU - Ellen Wiedtke
AU - Carolin Schmelas
AU - Dominik Miltner
AU - Alexander Rau
AU - Holger Erfle
AU - Hans-Georg Kräusslich
AU - Martin Müller
AU - Mavis Agbandje-Mckenna
AU - Dirk Grimm
PY - 2026
DA - 2026/09/30
JO - Molecular Therapy
DO - 10.1016/j.ymthe.2020.02.009
UR - https://hal.science/hal-05771967v1
AB - Display of short peptides on the surface of adeno-associated viruses (AAVs) is a powerful technology for the generation of gene therapy vectors with altered cell specificities and/or transduction efficiencies. Following its extensive prior use in the best characterized AAV serotype 2 (AAV2), recent reports also indicate the potential of other AAV isolates as scaffolds for peptide display. In this study, we systematically explored the respective capacities of 13 different AAV capsid variants to tolerate 27 peptides inserted on the surface followed by production of reporter-encoding vectors. Single-round screening in pre-arrayed 96-well plates permitted rapid and simple identification of superior vectors in >90 cell types, including T cells and primary cells. Notably, vector performance depended not only on the combination of capsid, peptide, and cell type, but also on the position of the inserted peptide and the nature of flanking residues. For optimal data availability and accessibility, all results were assembled in a searchable online database offering multiple output styles. Finally, we established a reverse-transduction pipeline based on vector pre-spotting in 96- or 384-well plates that facilitates high-throughput library panning. Our comprehensive illustration of the vast potential of alternative AAV capsids for peptide display should accelerate their in vivo screening and application as unique gene therapy vectors.
SN - 1525-0016
SN - 1525-0024
ER -