EGFR-Binding Peptides: From Computational Design towards Tumor-Targeting of Adeno-Associated Virus Capsids

Feiner R, Kemker I, Krutzke L, Allmendinger E, Mandell DJ, Sewald N, Kochanek S, Müller K (2020)
International Journal of Molecular Sciences 21(24): 9535.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Feiner, RebeccaUniBi; Kemker, IsabellUniBi; Krutzke, Lea; Allmendinger, Ellen; Mandell, Daniel J.; Sewald, NorbertUniBi ; Kochanek, Stefan; Müller, KristianUniBi
Abstract / Bemerkung
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.
Stichworte
cyclic peptide; VDEPT; oncolytic virus; protein engineering; VP protein; synthetic biology
Erscheinungsjahr
2020
Zeitschriftentitel
International Journal of Molecular Sciences
Band
21
Ausgabe
24
Art.-Nr.
9535
eISSN
1422-0067
Finanzierungs-Informationen
Open-Access-Publikationskosten wurden durch die Deutsche Forschungsgemeinschaft und die Universität Bielefeld gefördert.
Page URI
https://pub.uni-bielefeld.de/record/2949472

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Feiner R, Kemker I, Krutzke L, et al. EGFR-Binding Peptides: From Computational Design towards Tumor-Targeting of Adeno-Associated Virus Capsids. International Journal of Molecular Sciences. 2020;21(24): 9535.
Feiner, R., Kemker, I., Krutzke, L., Allmendinger, E., Mandell, D. J., Sewald, N., Kochanek, S., et al. (2020). EGFR-Binding Peptides: From Computational Design towards Tumor-Targeting of Adeno-Associated Virus Capsids. International Journal of Molecular Sciences, 21(24), 9535. doi:10.3390/ijms21249535
Feiner, R., Kemker, I., Krutzke, L., Allmendinger, E., Mandell, D. J., Sewald, N., Kochanek, S., and Müller, K. (2020). EGFR-Binding Peptides: From Computational Design towards Tumor-Targeting of Adeno-Associated Virus Capsids. International Journal of Molecular Sciences 21:9535.
Feiner, R., et al., 2020. EGFR-Binding Peptides: From Computational Design towards Tumor-Targeting of Adeno-Associated Virus Capsids. International Journal of Molecular Sciences, 21(24): 9535.
R. Feiner, et al., “EGFR-Binding Peptides: From Computational Design towards Tumor-Targeting of Adeno-Associated Virus Capsids”, International Journal of Molecular Sciences, vol. 21, 2020, : 9535.
Feiner, R., Kemker, I., Krutzke, L., Allmendinger, E., Mandell, D.J., Sewald, N., Kochanek, S., Müller, K.: EGFR-Binding Peptides: From Computational Design towards Tumor-Targeting of Adeno-Associated Virus Capsids. International Journal of Molecular Sciences. 21, : 9535 (2020).
Feiner, Rebecca, Kemker, Isabell, Krutzke, Lea, Allmendinger, Ellen, Mandell, Daniel J., Sewald, Norbert, Kochanek, Stefan, and Müller, Kristian. “EGFR-Binding Peptides: From Computational Design towards Tumor-Targeting of Adeno-Associated Virus Capsids”. International Journal of Molecular Sciences 21.24 (2020): 9535.
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2020-12-16T13:46:22Z
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