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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

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. Viola, Livia 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

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. More... »

PAGES

12538

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-30790-2

    DOI

    http://dx.doi.org/10.1038/s41598-018-30790-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1106187509

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30135446


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