[Effects of cationic vectors complexed with plasmid DNA on the phagosome-lysosome fusion in murine peritoneal macrophages and J744 macrophages].
Polyethylenimine (PEI) and cationic polypeptides complexed with plasmid DNA are the most efficient nonviral vectors for gene therapy. It is believed that endocytosis is the major pathway for cell entering by PEI/DNA or cationic peptides/DNA complexes. Effects of plasmid DNA complexed with PEI, poly-L-lysine (PLL), poly-D-lysine (PDL) and polyarginine (PA) on the phagosome-lysosome fusion (P-LF) were studied in murine peritoneal macrophages and J774 macrophages. Cationic polypeptide PLL can be hydrolysed by cellular peptidases, but its stereoisomer, PDL, cannot be split by these enzymes. PEI, PDL, and PA have been shown to inhibit P-LF. PLL showed a low effect on the P-LF. On the basis of these studies, we assume that lysosomotropic agents able to change functions of lysosomes in the cell may affect transfection efficiency and thus be used for gene therapy.
Mozhenok
T P
TP
Institute of Cytology RAS, St. Petersburg. mozhenok@mail.cytspb.rssi.ru
Leont'eva
E A
EA
Beliaeva
T N
TN
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004705:Endocytosis; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000502:physiology; D008247:Lysosomes / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010588:Phagosomes / Q000502:physiology*; D010957:Plasmids / Q000737:chemistry / Q000502:physiology*; D011094:Polyethyleneimine / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
D010455:Peptides; D011107:Polylysine; C015462:polyarginine; D011094:Polyethyleneimine; D010447:Peptide Hydrolases