Prolonged organ retention and safety of plasmid DNA administered in polyethylenimine complexes.
Polyethylenimine (PEI) has been studied as an efficient nonviral gene transfer vector. Here, we report the biodistribution fates and safety of plasmid DNA intravenously administered in PEI complexes. Using pCMVbeta as a model gene, the biodistribution of plasmid DNA was measured by quantitative polymerase chain reaction. A deletion mutant of pCMVbeta was used as an internal standard. After intravenous administration of PEI/DNA complexes, the serum levels of DNA rapidly declined for up to 15 min. However, after this point, the serum levels of DNA diminished slowly. At 15 min after dose, PEI/DNA complexes showed 33-fold higher distribution of DNA in the lung than did naked DNA. At 24 h, all the organs tested showed much higher levels of plasmid DNA in PEI/DNA complexes, with distribution in the liver and lung being three orders of magnitude higher than naked DNA. The mRNA expression of DNA was observed in various organs of PEI/DNA-treated mice at 12 days after dose. Once a week dosing of PEI/DNA complexes over 3 consecutive weeks did not alter the histology of the organs. However, twice a week dosing over 3 weeks induced a sign of inflammation in the liver. These results indicate that PEI enhances the delivery and retention of plasmid DNA in the organs, especially the liver, but that safe delivery requires proper dosing intervals.
Oh
Y K
YK
Department of Microbiology, College of Medicine, Pochon CHA University, Kyonggi-do, South Korea.
Kim
J P
JP
Yoon
H
H
Kim
J M
JM
Yang
J S
JS
Kim
C K
CK
D000818:Animals; D019540:Area Under Curve; D003587:Cytomegalovirus / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005822:Genetic Vectors / Q000493:pharmacokinetics*; D007249:Inflammation; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D051379:Mice; D010053:Ovary / Q000378:metabolism; D011094:Polyethyleneimine; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D019444:Vaccines, DNA / Q000493:pharmacokinetics
D012333:RNA, Messenger; D019444:Vaccines, DNA; D011094:Polyethyleneimine; D004247:DNA