Abstract
We have developed surface-shielded ligand-polycation based gene delivery systems which are able to target gene expression to distant tumors after systemic application. Tumor-specific targeting is achieved by (1) incorporation of cell-binding ligands; and (2) shielding of the complexes from non-specific interactions with blood components and non-target cells. Shielding of polycation/DNA complexes can be achieved by coating with either polyethylene glycol or by incorporating the ligand transferrin at high densities. Following systemic application, surface-shielded DNA complexes coding for a highly active, yet highly toxic cytokine, tumor necrosis factor-α (TNFα), localized gene expression to distant tumors, resulting in hemorrhagic tumor necrosis and inhibition of tumor growth. TNFα activity was confined to the tumor without systemic TNF-related toxicity. These results indicate that targeted gene delivery may be an attractive strategy to use highly potent molecules in cancer treatment.
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Kircheis, R., Wightman, L., Kursa, M. et al. Tumor-targeted gene delivery: an attractive strategy to use highly active effector molecules in cancer treatment. Gene Ther 9, 731–735 (2002). https://doi.org/10.1038/sj.gt.3301748
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DOI: https://doi.org/10.1038/sj.gt.3301748
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