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        Water-Soluble Cationic Methacrylate Polymers for Nonviral Gene Delivery

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        The aim of gene therapy is to treat inherited or acquired genetic deficiencies (e.g., cystic fibrosis) or viral diseases (e.g., hepatitis B, HIV) by introduction of DNA encoding a therapeutic protein or a specific virus antigen, respectively, into the nucleus of the target cell. Because naked DNA will barely pass cellular membranes, a carrier system is required for transfection (1 4 ). Cationic polymers, which condense DNA by ionic interaction, form a promising class of nonviral transfection agents. Well-known examples of these polymers are DEAE dextran, poly(L-lysine), poly(ethylenimine), and poly(2- [dimethylamino]ethyl methacrylate) (pDMAEMA) (5 10 ). In order to achieve transfection, aplasmid must be delivered into the nucleus, which requires cellular uptake of polymerDNA complexes, generally referred to as “polyplexes” (11 ), which most likely occurs via endocytosis, followed by endosomal escape and transport to the nucleus. The polyplex must dissociate, either in the cytosol or in the nucleus, which may be a critical step in the transfection process.
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