Hoffmann, Katrin and Milech, Nadia and Juraja, Suzy M. and Cunningham, Paula T. and Stone, Shane R. and Francis, Richard W. and Anastasas, Mark and Hall, Clinton M. and Heinrich, Tatjana and Bogdawa, Heique M. and Winslow, Scott and Scobie, Marie N. and Dewhurst, Robert E. and Florez, Laura and Ong, Ferrer and Kerfoot, Maria and Champain, Danie and Adams, Abbie M. and Fletcher, Susan and Viola, Helena M and Hool, Livia C and Connor, Theresa and Longville, Brooke A. C. and Tan, Yew-Foon and Kroeger, Karen and Morath, Volker and Weiss, Gregory A. and Skerra, Arne and Hopkins, Richard M. and Watt, Paul M. (2018) A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery. Scientific Reports, 8 (1). ISSN 2045-2322 (Not OA)
Full text not available from this repository.Abstract
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.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 26 Aug 2018 22:48 |
| Last Modified: | 26 Aug 2018 22:48 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/751 |
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