Negligible induction of IFN-gamma, IL-12 and TNF-alpha by DNA-PEI 750 kDa/albumin complexes.
A 750 kDa polyethylenimine (PEI 750 kDa) combined with albumin has been found to mediate in vivo a highly efficient transfection of small amounts of plasmid DNA. Using this exceptional carrier system we evaluated the inflammatory responses triggered by CpG sequences found in plasmid DNA. Using as little as 1 mug DNA transferred in vivo caused an almost negligible response from pro-inflammatory cytokines (IFN-gamma, IL-12 and TNF-alpha), as assessed in serum with a commercially available kit. Administering 750 kDa PEI/albumin/plasmid DNA complexes every three days assured a high and prolonged in vivo expression of a reporter protein. A further increase in the level of such protein was obtained by administering the investigated complexes concurrently with dexamethasone. High gene transfer capability and a relatively low pro-inflammatory response of 750 kDa PEI/albumin/DNA complexes can be exploited for recurrent gene transfer into lungs to treat (via inhalation or instillation) cancer or genetic disorders such as cystic fibrosis.
Smolarczyk
Ryszard
R
Department of Molecular Biology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland.
Cichoń
Tomasz
T
Sochanik
Aleksander
A
Szala
Stanisław
S
D000418:Albumins / Q000737:chemistry*; D000818:Animals; D016207:Cytokines / Q000097:blood*; D017930:Genes, Reporter; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D010957:Plasmids; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000418:Albumins; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D011094:Polyethyleneimine; D008156:Luciferases