BPS 2024
Amphiphilic Shuttle Peptides Enable PMO Delivery to Basal Cell Carcinoma and Airway Epithelia
David Guay
VP Innovation and Technology, Feldan Therapeutics
ABSTRACT
Cell penetrating peptides (CPPs) are short peptides generally carrying a net positive charge and typically covalently fused with cargos to mediate their internalization into cells. However, endosomal sequestration following CPP-mediated delivery often limits cytosolic availability of the cargo. To avoid the endosomal entrapment characteristic of CPP-mediated delivery, we designed the shuttle peptide by fusing an endosomal leakage domain (ELD) to a CPP domain connected by a poly-glycine linker. In contrast to standard strategies using CPPs, the shuttle peptide is not covalently linked to the cargo, but is co-incubated with a cargo, enabling its rapid cytoplasmic delivery without endosomal entrapment after a brief incubation with cells. Using the Feldan Shuttle to enable delivery of phosphorodiamidate morpholino oligomer (PMO) to skin tumor, Feldan Therapeutics is developing an efficient, non-surgical approach to treat basal cell carcinoma (BCC). This first-in-class non-invasive intralesional treatment selectively targets BCC cells by disrupting an intracellular component involved in the pathophysiology of the disease. In addition, as the shuttle peptide is highly effective for delivery to airway epithelial cells, Feldan is developing pulmonary treatments for muco-obstructive diseases.
BIO
David Guay is the VP Innovation and Technology at Feldan Therapeutics. Dr. Guay received his PhD in molecular and cell biology from Laval University and conducted a postdoctoral fellowship in chemical engineering at McGill University where he developed a DNA delivery technique based on a non-thermal plasma technology. He joined Feldan Therapeutics in 2009 where he led the development and optimization of the Shuttle peptide technology that enables delivery of small molecules, PMOs and proteins to cells, airway epithelia, and basal cell carcinoma.