Intraperitoneal linear polyethylenimine (L-PEI)-mediated gene delivery to ovarian carcinoma nodes in mice.
Linear polyethylenimine (L-PEI) is an efficient transfection agent for ovarian carcinoma cells in vitro and ex vivo. In the present work, we go a step further and evaluate the efficacy of L-PEI in human ovarian tumor nodes developed in mice. PEI/DNA complexes were administered intraperitoneally instead of intravenously to avoid sequestering of complexes in the lung and liver and to allow transfection of nonvascularized tumor nodes. Plasmid biodistribution was studied by PCR and gene expression was characterized using complementary luciferase and beta-galactosidase assays. Intraperitoneal (i.p.) injection of L-PEI/DNA complexes allowed the straightforward distribution of plasmid in the whole peritoneal cavity. Gene expression occurred in many organs, but tumor nodes appeared as preferential sites for transgene expression. The i.p. delivery route allowed repeated injections and administration of large amounts of DNA (up to 400 mug) without signs of toxicity, even for doses well beyond the intravenous lethal dose. Transgene expression was dose-dependent and transient. However, multiple injections allowed its persistence to increase. These results provide encouraging elements towards the development of PEI-based gene therapy protocols for the treatment of advanced stage ovarian carcinoma.
Louis
M-H
MH
Groupe Régional d'Etude sur le Cancer (GRECAN), Unité 'Biologie et Thérapies Innovantes des Cancers Localement Agressifs' et, Centre F. Baclesse, Caen cedex, France.
Dutoit
S
S
Denoux
Y
Y
Erbacher
P
P
Deslandes
E
E
Behr
J-P
JP
Gauduchon
P
P
Poulain
L
L
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D017930:Genes, Reporter; D015316:Genetic Therapy; D006801:Humans; D008156:Luciferases; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010957:Plasmids / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D014162:Transfection / Q000379:methods; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D011094:Polyethyleneimine; D008156:Luciferases; D001616:beta-Galactosidase