Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration
| Autor: | Jamie M. Bergen, Philip J. Horner, Russell N. Johnson, John Ravits, Heidi Back, Drew L. Sellers, Suzie H. Pun |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Central nervous system Peptide law.invention 03 medical and health sciences 0302 clinical medicine law In vivo medicine Recombinase Humans Motor Neurons chemistry.chemical_classification Multidisciplinary Integrases business.industry Biological Sciences Spinal cord Fusion protein Axons Protein Transport 030104 developmental biology medicine.anatomical_structure Spinal Cord chemistry Recombinant DNA Axoplasmic transport Peptides business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Proceedings of the National Academy of Sciences. 113:2514-2519 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1515526113 |
| Popis: | A significant unmet need in treating neurodegenerative disease is effective methods for delivery of biologic drugs, such as peptides, proteins, or nucleic acids into the central nervous system (CNS). To date, there are no operative technologies for the delivery of macromolecular drugs to the CNS via peripheral administration routes. Using an in vivo phage-display screen, we identify a peptide, targeted axonal import (TAxI), that enriched recombinant bacteriophage accumulation and delivered protein cargo into spinal cord motor neurons after intramuscular injection. In animals with transected peripheral nerve roots, TAxI delivery into motor neurons after peripheral administration was inhibited, suggesting a retrograde axonal transport mechanism for delivery into the CNS. Notably, TAxI-Cre recombinase fusion proteins induced selective recombination and tdTomato-reporter expression in motor neurons after intramuscular injections. Furthermore, TAxI peptide was shown to label motor neurons in the human tissue. The demonstration of a nonviral-mediated delivery of functional proteins into the spinal cord establishes the clinical potential of this technology for minimally invasive administration of CNS-targeted therapeutics. |
| Databáze: | OpenAIRE |
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