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  A triple chain polycationic peptide-mimicking amphiphile – efficient DNA-transfer without co-lipids.

Pinnapireddy, S. R., Giselbrecht, J., Strehlow, B., Janich, C., Husteden, C., Meister, A., et al. (2020). A triple chain polycationic peptide-mimicking amphiphile – efficient DNA-transfer without co-lipids. Biomaterials Science, 8(1), 232-249. doi:10.1039/c9bm01093a.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-3E3E-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-698F-5
Genre: Journal Article

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 Creators:
Pinnapireddy, Shashank Reddy, Author
Giselbrecht, Julia, Author
Strehlow, Boris, Author
Janich, Christopher, Author
Husteden, Catharina, Author
Meister, Annette, Author
Loppnow, Harald, Author
Sedding, Daniel, Author
Erdmann, Frank, Author
Hause, Gerd, Author
Brezesinski, Gerald1, Author              
Groth, Thomas, Author
Langner, Andreas, Author
Bakowsky, Udo, Author
Wolk, Christian, Author
Affiliations:
1Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863284              

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 Abstract: Non-viral gene delivery in its current form is largely dependent upon the ability of a delivery vehicle to protect its cargo in the extracellular environment and release it efficiently inside the target cell. Also a simple delivery system is required to simplify a GMP conform production if a marketing authorization is striven for. This work addresses these problems. We have developed a synthetic polycationic peptide-mimicking amphiphile, namely DiTT4, which shows efficient transfection rates and good biocompatibility without the use of a co-lipid in the formulation. The lipid-nucleic acid complex (lipoplex) was characterized at the structural (electron microscopy), physical (laser Doppler velocimetry and atomic force microscopy) and molecular levels (X-ray scattering). Stability studies of the lipoplexes in the presence of serum and heparin indicated a stable formation capable of protecting the cargo against the extracellular milieu. Hemocompatibility studies (hemolysis, complement activation and erythrocyte aggregation) demonstrated the biocompatibility of the formulation for systemic administration. The transfection efficiency was assessed in vitro using the GFP assay and confocal laser scanning microscopy studies. With the chorioallantoic membrane model, an animal replacement model according to the 3R strategy (replacement, refinement, and reduction), initial in vivo experiments were performed which demonstrate fast and efficient transfection in complex tissues and excellent biocompatibility.

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Language(s): eng - English
 Dates: 2019-10-232020
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: ISI: 31681923
DOI: 10.1039/c9bm01093a
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Title: Biomaterials Science
Source Genre: Journal
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Publ. Info: Cambridge : Royal Society of Chemistry
Pages: - Volume / Issue: 8 (1) Sequence Number: - Start / End Page: 232 - 249 Identifier: ISSN: 2047-4830