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, 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.     

Enhancing the Cellular Delivery of Nanoparticles Using Lipo‐Oligoarginine Peptides

Nanoparticles have great potential as nanotherapeutics, delivery vectors, and molecular imaging agents due to their flexible properties. Although intracellular and nuclear delivery of nanoparticles is desirable for therapeutic applications, it remains a challenge. Cell penetrating peptides (CPPs) are a powerful tool for the intracellular delivery of various cargoes. Here it is reported that functionalization of nanoparticles with a myristoylated oligoarginine CPP promotes cellular uptake without increased toxicity. It is evident that the myristoylated CPP is much more effective in transporting nanoparticles than the unmodified CPPs.