Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides
Protein transduction domains (PTDs) are powerful nongenetic tools that allow intracellular delivery of conjugated cargoes to modify cell behavior. Their use in biomedicine has been hampered by inefficient delivery to nuclear and cytoplasmic targets. Here we overcame this deficiency by developing a s...
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| Format: | Article |
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National Academy of Sciences
2016
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| Online Access: | https://eprints.nottingham.ac.uk/31456/ |
| _version_ | 1848794207512166400 |
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| author | Dixon, James E. Osman, Gizem Morris, Gavin E. Markides, Hareklea Rotherham, Michael Bayoussef, Zahia El-Haj, Alicia Denning, Chris Shakesheff, Kevin M. |
| author_facet | Dixon, James E. Osman, Gizem Morris, Gavin E. Markides, Hareklea Rotherham, Michael Bayoussef, Zahia El-Haj, Alicia Denning, Chris Shakesheff, Kevin M. |
| author_sort | Dixon, James E. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Protein transduction domains (PTDs) are powerful nongenetic tools that allow intracellular delivery of conjugated cargoes to modify cell behavior. Their use in biomedicine has been hampered by inefficient delivery to nuclear and cytoplasmic targets. Here we overcame this deficiency by developing a series of novel fusion proteins that couple a membrane-docking peptide to heparan sulfate glycosaminoglycans (GAGs) with a PTD. We showed that this GET (GAG-binding enhanced transduction) system could deliver enzymes (Cre, neomycin phosphotransferase), transcription factors (NANOG, MYOD), antibodies, native proteins (cytochrome C), magnetic nanoparticles (MNPs), and nucleic acids [plasmid (p)DNA, modified (mod)RNA, and small inhibitory RNA] at efficiencies of up to two orders of magnitude higher than previously reported in cell types considered hard to transduce, such as mouse embryonic stem cells (mESCs), human ESCs (hESCs), and induced pluripotent stem cells (hiPSCs). This technology represents an efficient strategy for controlling cell labeling and directing cell fate or behavior that has broad applicability for basic research, disease modeling, and clinical application. |
| first_indexed | 2025-11-14T19:12:31Z |
| format | Article |
| id | nottingham-31456 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:12:31Z |
| publishDate | 2016 |
| publisher | National Academy of Sciences |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-314562020-05-04T17:33:28Z https://eprints.nottingham.ac.uk/31456/ Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides Dixon, James E. Osman, Gizem Morris, Gavin E. Markides, Hareklea Rotherham, Michael Bayoussef, Zahia El-Haj, Alicia Denning, Chris Shakesheff, Kevin M. Protein transduction domains (PTDs) are powerful nongenetic tools that allow intracellular delivery of conjugated cargoes to modify cell behavior. Their use in biomedicine has been hampered by inefficient delivery to nuclear and cytoplasmic targets. Here we overcame this deficiency by developing a series of novel fusion proteins that couple a membrane-docking peptide to heparan sulfate glycosaminoglycans (GAGs) with a PTD. We showed that this GET (GAG-binding enhanced transduction) system could deliver enzymes (Cre, neomycin phosphotransferase), transcription factors (NANOG, MYOD), antibodies, native proteins (cytochrome C), magnetic nanoparticles (MNPs), and nucleic acids [plasmid (p)DNA, modified (mod)RNA, and small inhibitory RNA] at efficiencies of up to two orders of magnitude higher than previously reported in cell types considered hard to transduce, such as mouse embryonic stem cells (mESCs), human ESCs (hESCs), and induced pluripotent stem cells (hiPSCs). This technology represents an efficient strategy for controlling cell labeling and directing cell fate or behavior that has broad applicability for basic research, disease modeling, and clinical application. National Academy of Sciences 2016-01-05 Article PeerReviewed Dixon, James E., Osman, Gizem, Morris, Gavin E., Markides, Hareklea, Rotherham, Michael, Bayoussef, Zahia, El-Haj, Alicia, Denning, Chris and Shakesheff, Kevin M. (2016) Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides. Proceedings of the National Academy of Sciences, 113 (3). E291-E299. ISSN 1091-6490 http://www.pnas.org/content/113/3/E291 doi:10.1073/pnas.1518634113 doi:10.1073/pnas.1518634113 |
| spellingShingle | Dixon, James E. Osman, Gizem Morris, Gavin E. Markides, Hareklea Rotherham, Michael Bayoussef, Zahia El-Haj, Alicia Denning, Chris Shakesheff, Kevin M. Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides |
| title | Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides |
| title_full | Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides |
| title_fullStr | Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides |
| title_full_unstemmed | Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides |
| title_short | Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides |
| title_sort | highly efficient delivery of functional cargoes by the synergistic effect of gag binding motifs and cell-penetrating peptides |
| url | https://eprints.nottingham.ac.uk/31456/ https://eprints.nottingham.ac.uk/31456/ https://eprints.nottingham.ac.uk/31456/ |