Abstract
Successful gene therapy necessitates safe and efficient gene transfer. This article describes the use of a cationic polymer, which was synthesized by cross-linking low molecular weight branched poly(ethylenimine) (PEI) with both β-cyclodextrin and propane-1,2,3-triol, for efficient and safe non-viral gene delivery. Experimentation demonstrated that the polymer had a pH buffering capacity and DNA condensing ability comparable to those of PEI 25 kDa. In B16-F0 cells, the polymer increased the transfection efficiency of naked DNA by 700-fold and yielded better transfection efficiencies than Fugene HD (threefold higher) and PEI 25 kDa (fivefold higher). The high transfection efficiency of the polymer was not affected by the presence of serum during transfection. In addition to B16-F0 cells, the polymer enabled efficient transfection of HepG2 and U87 cells with low cytotoxicity. Our results indicated that our polymer is a safe and efficient transfection reagent that warrants further development for in vitro, in vivo and clinical applications.
Highlights
Gene delivery by viral and non-viral vectors is an important area of research due to its potential applications in gene therapy
CDI activated the hydroxyl groups of b-CyD, which in turn reacted with the primary amine groups of PEA to generate BPEA
Since the molecular weight cutoff (12.4 kDa) of the dialysis membrane used to isolate BPEA was much higher than the molecular weight of all reactants used throughout the experiments, the dialysis process affords the product in high purity
Summary
Gene delivery by viral and non-viral vectors is an important area of research due to its potential applications in gene therapy. Numerous nonviral gene delivery systems have been reported [1,2,3,4] Among these systems, poly(ethylenimine) (PEI) has gained special attention because of its high transfection efficiency [2]. Though bPEI 25 kDa exhibited high transfection efficiency, its toxicity was high The latter observation was supported by the 8.6% mortality rate in mice hours after nasal instillation of bPEI kDa [11]. Such high toxicity has impeded the practical application of bPEI 25 kDa
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