A sterically stabilized immunolipoplex for systemic administration of a therapeutic gene

Gene Therapy
Wei YuE H Chang

Abstract

A sterically stabilized immunolipoplex (TsPLP), containing an antitransferrin receptor single-chain antibody fragment (TfRscFv)-PEG molecule, has been developed to specifically and efficiently deliver a therapeutic gene to tumor cells. A postcoating preparation strategy was employed in which a DNA/lipid complex (lipoplex) was formed first and then sequentially conjugated with PEG and TfRscFv. The complex prepared by this method was shown to be superior in ability to deliver genes to tumor cells than when prepared by a common precoating strategy, in which DNA is mixed with TfRscFv-PEG conjugated liposome. Using prostate cancer cell line DU145, a comparison was made between the in vitro and in vivo gene delivery efficiencies of four complexes, Lipoplex (LP), PEG-Lipoplex (PLP), TfRscFv-PEG-Lipoplex (TsPLP) and our standard TfRscFv-Lipoplex (TsLP). In vitro, the order of transfection efficiency was TsLP>LP approximately TsPLP>PLP. However, in vivo the order of transfection efficiency, after systemic administration via the tail vein, was TsPLP>TsLP>LP or PLP with TsPLP-mediated exogenous gene expression in tumor being two-fold higher than when mediated by TsLP. This suggests that the in vitro transfection efficiency of TsPLP was no...Continue Reading

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