Supramolecular Peptide Nanofibrils with Optimized Sequences and Molecular Structures for Efficient Retroviral Transduction

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, we report the first sequence optimization of PNFs for enhanced retroviral gene transduction via a multiparameter and a multiscale approach. Retroviral gene transfer is the method of choice for 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 provided the structure parameters responsible for PNF assembly, fibril morphologies and PNF-virus-cell interactions. Optimized peptide sequences have been obtained quantitatively forming supramolecular nanofibrils with high intermolecular beta-sheet content that efficiently bound virions and attached to cellular membranes revealing efficient retroviral gene transfer