Abstract
Developments of non-viral carriers have headed toward reducing cytotoxicity, which results from the use of conventional gene carriers, and enhancing gene delivery efficiency. Cys-(d-R9)-Cys repeated reducible poly(oligo-D-arginine) (rPOA) is one of the most efficient non-viral carriers for gene therapy; however, while its efficiency has been verified in the lung and brain, it is necessary to confirm its activity in each organ or tissue since there are differences of gene carrier susceptibility to among tissue types. We therefore tested the compatibility of rPOA in cardiac tissue by in vitro or in vivo experiments and confirmed its high transfection efficiency and low cytotoxicity. Moreover, substantial regenerative effects were observed following transfection with rPOA/pVEGF expression vector complexes (79% decreased infarct size) compared to polyethyleneimine (PEI) (34% decreased infarct size) in a rat myocardial infarction (MI) model. These findings suggest that rPOA efficiently enables DNA transfection in cardiac tissue and can be used as a useful non-viral therapeutic gene carrier for gene therapy in ischemic heart disease.
Highlights
To examine the suitability of reducible poly(oligo-D-arginine) (rPOA) for cardiac gene delivery, H9c2 cardiomyocytes were transfected with different rPOA/plasmid DNA (pDNA) ratios (1:0.5, 1:1, 1:2, and 1:4) and analyzed by gel retardation assay
RPOA is one of the most effective non-viral carrier for gene delivery to cultured cells or tissues [10, 12]; the efficacy of gene carrier delivery varies according to the cell or tissue type
Gene expression levels in rPOA/pCMV-luc complexes transfected cells measured by luciferase assay showed a similar luciferase activity to that of PEI/pCMV-luc complex-transfected cells, but the analysis of GFP expression by flow cytometry yielded different results since the proteins expressed by transfected gene are the primary therapeutic mediators; a proper evaluation of gene therapy efficiency must be estimated by the amount of protein expressed by the entire cell population, rather than the percentage of cells that express the transfected gene
Summary
Non-viral carriers are subject to various limitations, such as low transfection efficiency and high toxicity, and temporal gene expression. To overcome these limitations, many researchers focused their efforts on developing optimized enhanced gene carriers [6]. The feasibility rPOA/plasmid DNA (pDNA) polyplex treatment for MI induced in rat hearts was investigated through a comparative analysis with conventional polyethyleneimine (PEI)/pDNA complexes. These results suggested that rPOA was a suitable carrier for ischemic heart gene therapy
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