Transgene delivery with a cationic lipid in the presence of amyloid beta (betaAP) peptide

The ability of a cationic lipid to deliver plasmid DNA (pDNA) in presence of the neurotoxic fragment of amyloid beta-peptide was evaluated. Pre-treatment of cells with betaAP (25-35) peptide resulted in a modest increase in transgene expression. When betaAP (25-35) peptide was mixed with the pDNA/liposome complex and used, the complexes lost their ability to transfect. However, the reverse sequenced betaAP (35-25) peptide demonstrated no significant differences in transgene expression in pre-treated cells, and in cells where betaAP (35-25) peptide was mixed with pDNA/liposome complexes and transfected. The amount of pDNA delivered to the cells was decreased in presence of betaAP (25-35) as measured with flow cytometry using fluorescently labeled liposomes. The decreased endocytosis may be due to their rod-like structure formation as demonstrated by electron microscopy and atomic force microscopy (AFM). These results demonstrate that betaAP (25-35) peptide may interfere with gene delivery with cationic systems.