Shifting AAV9 tropism by binding moiety insertion enhances transduction of tumor cell lines and human glioblastoma explants

Rothschild-Gronau C, Borchert P, Radukic MT, Haverkamp L, Coras R, Simon M, Müller KM (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 16

Article Number: 24908

Journal Issue: 1

DOI: 10.1038/s41598-026-62481-8

Abstract

Tumor-specific targeting remains a major obstacle for the development of precision cancer therapies. For several tumors and specifically glioblastoma (GBM), an aggressive brain tumor with poor prognosis, more effective treatments are urgently needed. Recombinant adeno-associated viruses (rAAVs), with their established clinical utility and mutational capsid plasticity, offer a promising platform for targeted delivery. We engineered and evaluated modified AAV capsids derived from the established AAV2 with HSPG-tropism knockdown and two less-characterized, tropism-reduced AAV9 variants. The epidermal growth factor receptor (EGFR), a tumor marker often overexpressed in GBM, was targeted by inserting an affibody (ZEGFR:1907). Also chlorotoxin (CLTX) was inserted, a peptide from scorpion venom reported to bind GBM. Transduction efficiencies were initially assessed with established cell lines (A431, HeLa, U251MG, MCF7). Affibody-displaying capsids exhibited EGFR-dependent transduction, with AAV9-affibody variants surpassing AAV9 wild-type. Several affibody-displaying capsids also transduced patient-derived GBM explants, as confirmed by fluorescence microscopy. These findings highlight the potential of retargeting AAV9 variants and the use of human surgical tissue samples for the initial evaluation of newly designed AAV capsids.

Authors with CRIS profile

Roland Coras Institute of Neuropathology

Involved external institutions

Universität Bielefeld

Germany (DE)

How to cite

APA:

Rothschild-Gronau, C., Borchert, P., Radukic, M.T., Haverkamp, L., Coras, R., Simon, M., & Müller, K.M. (2026). Shifting AAV9 tropism by binding moiety insertion enhances transduction of tumor cell lines and human glioblastoma explants. Scientific Reports, 16(1). https://doi.org/10.1038/s41598-026-62481-8

MLA:

Rothschild-Gronau, Claire, et al. "Shifting AAV9 tropism by binding moiety insertion enhances transduction of tumor cell lines and human glioblastoma explants." Scientific Reports 16.1 (2026).

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