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.
Ajmani
P S
PS
Department of Pharmaceutics, University of Florida, Gainesville 32610, USA.
Wang
W
W
Tang
F
F
King
M A
MA
Meyer
E M
EM
Hughes
J A
JA
D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000008:administration & dosage*; D004705:Endocytosis; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D006801:Humans; D008055:Lipids / Q000008:administration & dosage*; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000378:metabolism; D010957:Plasmids; D051381:Rats; D019076:Transgenes; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D008055:Lipids; D010446:Peptide Fragments; C113041:amyloid beta-protein (35-25); D004247:DNA