Cell-penetrating peptides: an uptake mechanism & a new endosomolytic peptide
2013 (English)Licentiate thesis, comprehensive summary (Other academic)
Peptide-based drugs have slowly begun migrating from laboratories into pharmacies and now there are several on the market. However, currently only one gene based therapy that is relies on a viral delivery vector has been approved. The long-term goal of our research is to leverage the cell-penetrating peptide (CPP) technology into a potent, safe and simple delivery vector for oligonucleotide (ON) based therapies.
Cell-penetrating peptides have been actively researched for more than 20 years, and many CPPs have been discovered. However, it is not fully understood how the peptides are able to enter cells. In this thesis we present a novel receptor for CPP:ON complexes. Pharmacological inhibition and siRNA knockdown of the class A scavenger receptors (SCARAs) demonstrate that these receptors are the main pathway by which CPP:ON complexes are taken up. As the intracellular fate of particles taken up by (receptor mediated) endocytosis is entrapment in endosomes this thesis also presents a new peptide for ON delivery that has endosomolytic properties. Additionally this new peptide (PepFect 15) is also taken up via receptor-mediated endocytosis by the SCARAs.
Place, publisher, year, edition, pages
Stockholm: Department of Neurochemistry, Stockholm University , 2013.
Research subject Neurochemistry with Molecular Neurobiology
IdentifiersURN: urn:nbn:se:su:diva-94377ISBN: 978-91-7447-782-5OAI: oai:DiVA.org:su-94377DiVA: diva2:653423
2013-10-24, Heilbronnsalen, Department of Neurochemistry, Stockholm, 14:00 (English)
Barth, Andreas, Professor
Langel, Ülo, Professor
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