A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery
| العنوان: | A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery |
|---|---|
| المؤلفون: | Paula T. Cunningham, Mark Anastasas, Tatjana Heinrich, Laura Florez, Danie Champain, Theresa Connor, Paul M. Watt, Nadia Milech, Scott Winslow, Abbie M. Adams, Karen M. Kroeger, Richard W. Francis, Brooke A. C. Longville, Robert E. Dewhurst, Shane R. Stone, Yew Foon Tan, M. Scobie, Clinton M. Hall, Helena M. Viola, Maria Kerfoot, Livia C. Hool, Heique M. Bogdawa, Arne Skerra, Katrin Hoffmann, Ferrer Ong, Volker Morath, Suzy M. Juraja, Sue Fletcher, Gregory A. Weiss, Richard Hopkins |
| المصدر: | Scientific reports, vol 8, iss 1 Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-16 (2018) |
| بيانات النشر: | eScholarship, University of California, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cell, Druggability, Drug Evaluation, Preclinical, lcsh:Medicine, Cell-Penetrating Peptides, Inbred C57BL, Mice, 0302 clinical medicine, Drug Delivery Systems, Bacteriophage T7, Carbon-Nitrogen Ligases, Muscular Dystrophy, lcsh:Science, Microscopy, Multidisciplinary, Chemistry, Escherichia coli Proteins, Circular Dichroism, Preclinical, Other Physical Sciences, medicine.anatomical_structure, 5.1 Pharmaceuticals, 030220 oncology & carcinogenesis, Biotinylation, Development of treatments and therapeutic interventions, Intracellular, Endosome, Computational biology, CHO Cells, Article, Fluorescence, 03 medical and health sciences, Cricetulus, Rare Diseases, Peptide Library, medicine, Animals, Humans, Peptide library, Animal, HEK 293 cells, lcsh:R, Duchenne, Mice, Inbred C57BL, Muscular Dystrophy, Duchenne, Repressor Proteins, Disease Models, Animal, 030104 developmental biology, HEK293 Cells, Orphan Drug, Microscopy, Fluorescence, Cytoplasm, Disease Models, Drug Evaluation, lcsh:Q, Biochemistry and Cell Biology, Generic health relevance |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2982281cc58305b13bc410a28e61452e https://escholarship.org/uc/item/9539k69b |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2982281cc58305b13bc410a28e61452e |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |