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A new rapid cell-penetrating peptide based strategy to produce bacterial ghosts for plasmid delivery
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0001-8947-6643
2008 (English)In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 132, no 1, 49-54 p.Article in journal (Refereed) Published
Abstract [en]

The production of bacterial ghosts involves the lysis gene E plasmid in order to lyse and empty the bacteria of their cytoplasmic contents. After lysis the ghosts can either be loaded with new desired DNA and used for delivery to mammalian cells or used in vaccination. Cell-penetrating peptides have been used as delivery vehicles of drugs and oligonucleotides. Although many of them show low toxicity they have been compared to antimicrobial peptides involved in innate immunity. Recently we showed that cell-penetrating peptides also could be antimicrobial. In this study we take advantage of the antimicrobial effect of one cell-penetrating peptide, namely MAP, which is a model amphipathic peptide and treat bacteria with the peptide to produce bacterial ghosts. This new peptide based strategy is not dependent on the lysis gene E plasmid thus; several tiresome steps are removed in the production of ghosts. In addition the ghosts can be preloaded with a desired plasmid or DNA further removing time consuming reprocessing steps. To our knowledge this is the first study that uses a cell-penetrating peptide based strategy to produce bacterial ghosts to be used in plasmid delivery.

Place, publisher, year, edition, pages
2008. Vol. 132, no 1, 49-54 p.
Keyword [en]
Cell-penetrating peptides, Protein transduction domains, Bacterial ghosts, Delivery vehicle, Gene delivery
National Category
Chemical Sciences
URN: urn:nbn:se:su:diva-25533DOI: 10.1016/j.jconrel.2008.08.011ISI: 000261354400008OAI: diva2:199914
Available from: 2008-10-23 Created: 2008-10-07 Last updated: 2015-03-09Bibliographically approved
In thesis
1. Design and evaluation of drug delivery vehicles
Open this publication in new window or tab >>Design and evaluation of drug delivery vehicles
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A crucial aspect of drug delivery is efficient transport to the site of action. Thus, there is a need to design and evaluate new delivery vehicles. In this thesis two delivery vehicles, cell-penetrating peptides and bacterial ghosts, were evaluated. The understanding of the internalization and degradation kinetics of cell-penetrating peptides is important for the practical aspects of cargo delivery since peptides have a notorious reputation of being rapidly degraded. If the cell-penetrating peptide remains intact inside the cellular environment, there is a possibility that the peptide-cargo conjugate leaks back to the extracellular environment. However, if it is degraded outside the cell, the cargo will never be delivered. In order to improve uptake efficiency and to be able to foresee side effects, the translocation mechanism needs to be fully elucidated. Data gathered from the first two papers led to the proposal of a new me-chanism involved in cell-penetrating peptide uptake: the membrane repair response, a resealing mechanism rapidly patching up broken membranes. This mechanism could explain the divergence in perception concerning the uptake pathways. Furthermore a new assay to produce the second delivery vehicle, bacterial ghosts, was developed based on data from the cell-penetrating peptide investigations. Bacterial ghosts are dead bacteria devoid of cytoplasmic contents but still retaining their structural and morphological characteristics, after protein E lysis of the bacterial cell membrane. By using a cell-penetrating peptide with antimicrobial effects, a new rapid peptide-based strategy to produce ghosts was developed and the capability to deliver plasmid DNA into the cell for expression was evaluated.

Place, publisher, year, edition, pages
Stockholm: Institutionen för neurokemi, 2008. 77 p.
National Category
Research subject
Neurochemistry and Neurotoxicology
urn:nbn:se:su:diva-8256 (URN)978-91-7155-754-4 (ISBN)
Public defence
2008-11-14, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 13:00
Available from: 2008-10-23 Created: 2008-10-07Bibliographically approved

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Hällbrink, Mattias
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