A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery

Katrin Hoffmann, Nadia Milech, Suzy M. Juraja, Paula T. Cunningham, Shane R. Stone, Richard W. Francis, Mark Anastasas, Clinton M. Hall, Tatjana Heinrich, Heique M. Bogdawa, Scott Winslow, Marie N. Scobie, Robert E. Dewhurst, Laura Florez, Ferrer Ong, Maria Kerfoot, Danie Champain, Abbie M. Adams, Susan Fletcher, Helena M. ViolaLivia C. Hool, Theresa Connor, Brooke A.C. Longville, Yew Foon Tan, Karen Kroeger, Volker Morath, Gregory A. Weiss, Arne Skerra, Richard M. Hopkins, Paul M. Watt

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Cell penetrating peptides (CPPs) offer great potential to deliver therapeutic molecules to previously inaccessible intracellular targets. However, many CPPs are inefficient and often leave their attached cargo stranded in the cell’s endosome. We report a versatile platform for the isolation of peptides delivering a wide range of cargos into the cytoplasm of cells. We used this screening platform to identify multiple “Phylomer” CPPs, derived from bacterial and viral genomes. These peptides are amenable to conventional sequence optimization and engineering approaches for cell targeting and half-life extension. We demonstrate potent, functional delivery of protein, peptide, and nucleic acid analog cargos into cells using Phylomer CPPs. We validate in vivo activity in the cytoplasm, through successful transport of an oligonucleotide therapeutic fused to a Phylomer CPP in a disease model for Duchenne’s muscular dystrophy. This report thus establishes a discovery platform for identifying novel, functional CPPs to expand the delivery landscape of druggable intracellular targets for biological therapeutics.

Original languageEnglish
Article number12538
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Dec 2018


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