Cell-penetrating peptides: current landscape & future applications
Francesca Milletti
Principal Scientist, Roche
The potential of therapeutic modalities like peptides, oligonucleotides and antibodies is limited by their inability to cross the cell membrane and reach the cytosol, where most drug targets are. Tools that could address this bottleneck are poised to create a breakthrough for drug discovery. Unlike most peptides, cell-penetrating peptides have the ability to cross the cell membrane, and carry other large molecules with them, but many questions remain unsolved: to what extent do they reach the cytosol while remaining intact? What is the mechanism of action to gain cell entry? And under which conditions do they cross the cell membrane? I will discuss the current landscape of cell-penetrating peptides, illustrate design strategies to increase cell-permeability and proteolitic stability, and present recent advancements to detect cytosolic uptake of intact peptides based on a novel complementation assay.
Francesca Milletti is a Principal Scientist at Roche Innovation Center New York. She received her PhD in Chemistry from University of Perugia, Italy, where she developed a widely used computational program to predict the pKa of small molecules, MoKa. Before joining Roche, Francesca was a visiting student at UCSF and worked as a postdoc at Novartis in Basel.
At Roche, Francesca has developed new computational methods to study structure-activity relationships for small molecules and peptides. Working at the interface of chemistry and biology, she is now involved in the analysis of patient genomic data - with a special focus on cancer immunotherapy - and in the evaluation of external assets for Roche.