Abstract
A novel cationic polymer, dextran-spermine (D-SPM), has been found to mediate gene expression in a wide variety of cell lines and in vivo through systemic delivery. Here, we extended the observations by determining the optimal conditions for gene expression of D-SPM/plasmid DNA (D-SPM/pDNA) in cell lines and in the lungs of BALB/c mice via instillation delivery. In vitro studies showed that D-SPM could partially protect pDNA from degradation by nuclease and exhibited optimal gene transfer efficiency at D-SPM to pDNA weight-mixing ratio of 12. In the lungs of mice, the levels of gene expression generated by D-SPM/pDNA are highly dependent on the weight-mixing ratio of D-SPM to pDNA, amount of pDNA in the complex, and the assay time postdelivery. Readministration of the complex at day 1 following the first dosing showed no significant effect on the retention and duration of gene expression. The study also showed that there was a clear trend of increasing size of the complexes as the amount of pDNA was increased, where the sizes of the D-SPM/pDNA complexes were within the nanometer range.
Highlights
The success of gene therapy has largely depended upon the development of delivery vectors, which are able to efficiently and selectively deliver genes to target cells
Gene transfection efficiency was measured as a function of D-SPM/plasmid DNA (pDNA) weight-mixing ratio and expressed as relative light unit (RLU) normalized to total cells protein
This paper demonstrates that dextran-spermine (D-SPM) gene delivery into the lung resulted in modest level of reporter gene expression as compared to the control animals
Summary
The success of gene therapy has largely depended upon the development of delivery vectors, which are able to efficiently and selectively deliver genes to target cells. Viral vectors are able to mediate gene transfer with high efficiency with the possibility of long-term gene expression. Their broad use is affected by the limited size of the genetic material that can be delivered and the possibility of insertional mutagenesis [1]. In light of these concerns, nonviral gene delivery has emerged as a promising alternative. A significant number of cationic polymers in linear or branched configuration have been
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