Cargo Delivery into the Brain by in vivo identified Transport Peptides
| Autor: | Roland Schmucki, Hansruedi Loetscher, Helmut Jacobsen, Ulrich Certa, Martin Ebeling, Nadine Ruderisch, Eduard Urich, Eric A. Kitas, Christophe Schweitzer, Alessandra Bergadano, Per-Ola Freskgard |
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| Rok vydání: | 2015 |
| Předmět: |
T7 phage
Amino Acid Motifs Peptide Pharmacology Biology Blood–brain barrier Cisterna magna Article Cerebrospinal fluid Peptide Library In vivo Bacteriophage T7 medicine Animals Aspartic Acid Endopeptidases Position-Specific Scoring Matrices Amino Acid Sequence Peptide library Peptide sequence chemistry.chemical_classification Multidisciplinary Brain Reproducibility of Results Biological Transport biology.organism_classification Rats medicine.anatomical_structure Biochemistry chemistry Blood-Brain Barrier Amyloid Precursor Protein Secretases Cell Surface Display Techniques Peptides |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The blood-brain barrier and the blood-cerebrospinal fluid barrier prevent access of biotherapeutics to their targets in the central nervous system and therefore prohibit the effective treatment of neurological disorders. In an attempt to discover novel brain transport vectors in vivo, we injected a T7 phage peptide library and continuously collected blood and cerebrospinal fluid (CSF) using a cisterna magna cannulated conscious rat model. Specific phage clones were highly enriched in the CSF after four rounds of selection. Validation of individual peptide candidates showed CSF enrichments of greater than 1000-fold. The biological activity of peptide-mediated delivery to the brain was confirmed using a BACE1 peptide inhibitor linked to an identified novel transport peptide which led to a 40% reduction of Amyloid-β in CSF. These results indicate that the peptides identified by the in vivo phage selection approach could be useful transporters for systemically administrated large molecules into the brain with therapeutic benefits. |
| Databáze: | OpenAIRE |
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