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

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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.

Graphical abstract: A triple chain polycationic peptide-mimicking amphiphile – efficient DNA-transfer without co-lipids

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Publication details

The article was received on 14 Jul 2019, accepted on 20 Oct 2019 and first published on 23 Oct 2019


Article type: Paper
DOI: 10.1039/C9BM01093A
Biomater. Sci., 2020, Advance Article

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

    S. R. Pinnapireddy, J. Giselbrecht, B. Strehlow, C. Janich, C. Husteden, A. Meister, H. Loppnow, D. Sedding, F. Erdmann, G. Hause, G. Brezesinski, T. Groth, A. Langner, U. Bakowsky and C. Wölk, Biomater. Sci., 2020, Advance Article , DOI: 10.1039/C9BM01093A

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