EGFR-binding peptides: from computational design towards tumor-targeting of adeno-associated virus capsids
Feiner, Rebecca C.
Mandell, Daniel J.
International Journal of Molecular Sciences ; 21 (2020), 24. - Art.-Nr. 9535. - eISSN 1422-0067
Link to original publicationhttps://dx.doi.org/10.3390/ijms21249535
InstitutionsUKU. Abteilung für Gentherapie
Document versionpublished version (publisher's PDF)
The epidermal growth factor receptor (EGFR) plays a central role in the progression of many solid tumors. We used this validated target to analyze the de novo design of EGFR-binding peptides and their application for the delivery of complex payloads via rational design of a viral vector. Peptides were computationally designed to interact with the EGFR dimerization interface. Two new peptides and a reference (EDA peptide) were chemically synthesized, and their binding ability characterized. Presentation of these peptides in each of the 60 capsid proteins of recombinant adeno-associated viruses (rAAV) via a genetic based loop insertion enabled targeting of EGFR overexpressing tumor cell lines. Furthermore, tissue distribution and tumor xenograft specificity were analyzed with systemic injection in chicken egg chorioallantoic membrane (CAM) assays. Complex correlations between the targeting of the synthetic peptides and the viral vectors to cells and in ovo were observed. Overall, these data demonstrate the potential of computational design in combination with rational capsid modification for viral vector targeting opening new avenues for viral vector delivery and specifically suicide gene therapy.
Is supplemented byhttps://www.mdpi.com/1422-0067/21/24/9535/s1
Subject headings[GND]: Cyclopeptide | Proteindesign | Synthetische Biologie
[LCSH]: Cyclic peptides | Protein engineering | Synthetic biology
[MeSH]: Oncolytic Viruses
[Free subject headings]: VDEPT | VP protein
[DDC subject group]: DDC 570 / Life sciences | DDC 610 / Medicine & health
LicenseCC BY 4.0 International
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Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-47785
Feiner, Rebecca C. et al. (2023): EGFR-binding peptides: from computational design towards tumor-targeting of adeno-associated virus capsids. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-47785
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