Supramolecular peptide nanofibrils with optimized sequences and molecular structures for efficient retroviral transduction

Stefanie Sieste, Thomas Mack, Edina Lump, Manuel Hayn, Desiree Schutz, Annika Rocker, Christoph Meier, Kubra Kaygisiz, Frank Kirchhoff, Tuomas P.J. Knowles, Francesco S. Ruggeri, Christopher V. Synatschke, Jan Munch, Tanja Weil

Research output: Contribution to journalArticleAcademicpeer-review

Abstract



Amyloid‐like peptide nanofibrils (PNFs) are abundant in nature providing rich bioactivities and playing both functional and pathological roles. The structural features responsible for their unique bioactivities are, however, still elusive. Supramolecular nanostructures are notoriously challenging to optimize, as sequence changes affect self‐assembly, fibril morphologies, and biorecognition. Herein, the first sequence optimization of PNFs, derived from the peptide enhancing factor‐C (EF‐C, QCKIKQIINMWQ), for enhanced retroviral gene transduction via a multiparameter and a multiscale approach is reported. Retroviral gene transfer is the method of choice for the stable delivery of genetic information into cells offering great perspectives for the treatment of genetic disorders. Single fibril imaging, zeta potential, vibrational spectroscopy, and quantitative retroviral transduction assays provide the structure parameters responsible for PNF assembly, fibrils morphology, secondary and quaternary structure, and PNF‐virus‐cell interactions. Optimized peptide sequences such as the 7‐mer, CKFKFQF, have been obtained quantitatively forming supramolecular nanofibrils with high intermolecular β‐sheet content that efficiently bind virions and attach to cellular membranes revealing efficient retroviral gene transfer.
Original languageEnglish
Article number2009382
Number of pages12
JournalAdvanced Functional Materials
DOIs
Publication statusE-pub ahead of print - 22 Feb 2021

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