The effect of CpG motifs on gene expression and clearance kinetics of aerosol administered polyethylenimine (PEI)-plasmid DNA complexes in the lung.

Presence of CpG motifs within pDNA is widely reported to influence transgene expression as well as inflammatory response to nonviral gene vector complexes. Here, we analyzed gene expression kinetics and lung clearance after aerosol delivery of polyethylenimine (PEI) complexes with two different plasmid vectors: a first generation plasmid, pCMVLuc, and a plasmid with depleted CpG motifs, pCpG-free-Luc. After aerosol delivery, equal nanogram amounts of PEI-pDNA complexes were deposited in murine lungs.

CpG-free plasmid DNA prevents deterioration of pulmonary function in mice.

Nonviral gene vectors have been shown to be therapeutically effective in various animal models of inherited and acquired lung diseases. Although an acute unmethylated CG dinucleotide (CpG)-mediated inflammatory response has been previously observed for first-generation plasmids, its effect on pulmonary function has not been investigated to date. Here, we present data on lung functional parameters together with histopathology, cellular and inflammatory events in response to pulmonary administration of DNA-containing particles.

Thyroid hormone (T3)-modification of polyethyleneglycol (PEG)-polyethyleneimine (PEI) graft copolymers for improved gene delivery to hepatocytes.

Targeting of gene vectors to liver hepatocytes could offer the opportunity to cure various acquired and inherited diseases. Efficient gene delivery to the liver parenchyma has been obscured from efficient targeting of hepatocytes. Here we show that the thyroid hormone, triiodothyronine (T3), can be used to improve the gene transfer efficiency of nonviral gene vectors to hepatocytes in vitro and to the liver of mice in vivo.

Aerosol gene delivery to the murine lung is mouse strain dependent.

The cationic polymer polyethylenimine (PEI) has been previously demonstrated to efficiently deliver genes to the lungs of mice in vivo via nebulization. Although within these studies various mouse strains were used in individual experiments, no direct comparison of gene delivery to different mouse strains via aerosol application has been published to date. With respect to the widespread use of mice as animal models of inherited and acquired diseases, such data could be of relevance to select the most appropriate mouse genetic background for preclinical mouse models.