Journal article
A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery
Scientific Reports, Vol.8(1)
2018
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.
Details
- Title
- A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery
- Authors/Creators
- K. Hoffmann (Author/Creator)N. Milech (Author/Creator)S.M. Juraja (Author/Creator)P.T. Cunningham (Author/Creator)S.R. Stone (Author/Creator)R.W. Francis (Author/Creator)M. Anastasas (Author/Creator)C.M. Hall (Author/Creator)T. Heinrich (Author/Creator)H.M. Bogdawa (Author/Creator)S. Winslow (Author/Creator)M.N. Scobie (Author/Creator)R.E. Dewhurst (Author/Creator)L. Florez (Author/Creator)F. Ong (Author/Creator)M. Kerfoot (Author/Creator)D. Champain (Author/Creator)A.M. Adams (Author/Creator)S. Fletcher (Author/Creator)H.M. Viola (Author/Creator)L.C. Hool (Author/Creator)T. Connor (Author/Creator)B.A.C. Longville (Author/Creator)Y-F Tan (Author/Creator)K. Kroeger (Author/Creator)V. Morath (Author/Creator)GA. Weiss (Author/Creator)A. Skerra (Author/Creator)R.M. Hopkins (Author/Creator)P.M. Watt (Author/Creator)
- Publication Details
- Scientific Reports, Vol.8(1)
- Publisher
- Nature Publishing Group
- Identifiers
- 991005544363907891
- Murdoch Affiliation
- Centre for Comparative Genomics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 2 Chemistry
- 2.53 Polymers & Macromolecules
- 2.53.70 Nanocarrier Drug Delivery
- Web Of Science research areas
- Biochemistry & Molecular Biology
- ESI research areas
- Biology & Biochemistry