CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression.
Hyde SC., Pringle IA., Abdullah S., Lawton AE., Davies LA., Varathalingam A., Nunez-Alonso G., Green A-M., Bazzani RP., Sumner-Jones SG., Chan M., Li H., Yew NS., Cheng SH., Boyd AC., Davies JC., Griesenbach U., Porteous DJ., Sheppard DN., Munkonge FM., Alton EWFW., Gill DR.
Pulmonary delivery of plasmid DNA (pDNA)/cationic liposome complexes is associated with an acute unmethylated CG dinucleotide (CpG)-mediated inflammatory response and brief duration of transgene expression. We demonstrate that retention of even a single CpG in pDNA is sufficient to elicit an inflammatory response, whereas CpG-free pDNA vectors do not. Using a CpG-free pDNA expression vector, we achieved sustained (>or=56 d) in vivo transgene expression in the absence of lung inflammation.