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PepFect15, a novel endosomolytic cell-penetrating peptide for non-covalent oligonucleotide delivery
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0001-7746-8574
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0002-1228-9927
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.
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(English)Manuscript (preprint) (Other academic)
Keyword [en]
cell-penetrating peptide, drug delivery, oligonucleotide
National Category
Chemical Sciences
Research subject
Neurochemistry with Molecular Neurobiology
Identifiers
URN: urn:nbn:se:su:diva-74368OAI: oai:DiVA.org:su-74368DiVA: diva2:508497
Available from: 2012-03-08 Created: 2012-03-08 Last updated: 2016-01-29Bibliographically approved
In thesis
1. Cell-penetrating peptides and oligonucleotide delivery
Open this publication in new window or tab >>Cell-penetrating peptides and oligonucleotide delivery
2012 (English)Licentiate thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Stockholm: Department of Neurochemistry, Stockholm University, 2012. 25 p.
National Category
Biological Sciences Chemical Sciences
Research subject
Neurochemistry with Molecular Neurobiology
Identifiers
urn:nbn:se:su:diva-79060 (URN)978-91-7447-530-2 (ISBN)
Opponent
Supervisors
Available from: 2012-08-28 Created: 2012-08-24 Last updated: 2015-03-16Bibliographically approved
2. Rational design of novel cell-penetrating peptides
Open this publication in new window or tab >>Rational design of novel cell-penetrating peptides
2012 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Although cell-penetrating peptides (CPPs) have been an active field of research for over 20 years there are still properties such as efficiency and stability that must be improved for CPPs to reach their full potential as delivery vectors.

In this thesis two peptides were designed for non-covalent oligonucleotide delivery, in an attempt to overcome two major issues hampering wider use of CPPs, namely low stability and endosomal entrapment.

In Paper I we designed a new peptide named PepFect14, which has unnatural amino-acid ornithine as the source of positive charge, to address the stability issue. PepFect14 was shown to deliver SCOs in a highly efficient manner into different cell-lines. Furthermore, formulation of non-covalent PepFect14:SCO complexes into solid form, suitable for storage and transportation, was developed. The formulated complexes were stable for weeks and retained high activity.

In Paper II we modified PepFect14 with endosomolytic groups to facilitate endosomal escape, the resulting peptide was named PepFect15. Delivery of SCO and miRNA was efficiently mediated by PepFect15 into HeLa cells and endosomolytic property was validated. Additionally, uptake of Pepfect15:SCO complexes was shown to be mediated by scavenger receptor class A.

Place, publisher, year, edition, pages
Stockholm: Stockholm University, 2012
National Category
Chemical Sciences
Research subject
Neurochemistry with Molecular Neurobiology
Identifiers
urn:nbn:se:su:diva-80474 (URN)978-91-7447-475-6 (ISBN)
Presentation
2012-03-30, Heilbronnsalen, Svante Arrhenius väg 21A, Stockholm, 13:30 (English)
Opponent
Supervisors
Available from: 2012-10-30 Created: 2012-09-20 Last updated: 2017-11-28Bibliographically approved

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