TY  - JOUR
AB  - 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.
DA  - 2020
DO  - 10.3390/ijms21249535
KW  - cyclic peptide
KW  - VDEPT
KW  - oncolytic virus
KW  - protein engineering
KW  - VP protein
KW  - synthetic biology
LA  - eng
IS  - 24
PY  - 2020
T2  - International Journal of Molecular Sciences
TI  - EGFR-Binding Peptides: From Computational Design towards Tumor-Targeting of Adeno-Associated Virus Capsids
UR  - https://nbn-resolving.org/urn:nbn:de:0070-pub-29494728
Y2  - 2024-11-22T03:39:52
ER  -