Aim of the P2P CPP project
The P2P CPP project was initiated by STIpe therapeutics and the team aims to develop a safe and efficient means of getting drugs into cells.
Optimization of cell-penetrating peptides to enable therapeutics with intracellular targets (P2P CPP)
Numerous bioactive molecules with therapeutic potential have been developed for intracellular targets. Still, if the drug is unable to pass the cell membrane, like, e.g., most peptides and nucleic acids, it will never reach its target. Thus, there is a huge unmet need for methods that make the majority of the proteome, the intracellular targets, drugable by biologics.
An extensively studied way for macromolecules to reach the cytoplasm is to conjugate them to a small cell-penetrating peptide (CPP). This method is simple to use and safe and effective in cultures, but no CPP-conjugated drug has yet obtained marketing approval despite its great potential. In contrast to cell culture studies, intravenously injected conjugated CPPs have shown acute toxicity.
The P2P CPP team has developed two initial assays using physiologically relevant concentrations and timescales to reflect the toxicity, determining a reversible inward current and induction of vasodilation in a rat resistance artery. By testing an array of CPP conjugates, the team will look for a correlation between the peptide physicochemical properties and its safety profile. The first success criterion will be to determine if their in vitro assays are indeed predictive of toxicity. That would enable improved safety, and, ultimately, the best possible direct outcome would be a CPP-based novel cancer therapy.
The project is, in its essence, an open collaboration initiated by STipe when they recognized the need for an improved basic molecular and physiological understanding of how CPPs work.
AU: Hanne Poulsen, Department of Molecular Biology and Genetics
AU: Ulf Simonsen, Department of Biomedicine
AU: Daniel Otzen, iNANO/Department of Molecular Biology and Genetics
STipe Therapeutics ApS: Claus Olesen and Richard Bethell
ApconiX Ltd: Michael Morton