| Polyethylenimine (PEI) is one of the most efficient and widely studied synthetic carriers for delivery of plasmid DNA into cells in vitro and in vivo. The high transfection efficiency of PEI/DNA complexes has been ascribed to the capacity of PEI to buffer endosomes, which protects DNA from nuclease degradation and facilitates endosomal escape of PEI/DNA complexes ("proton sponge hypothesis"). Further studies have shown that the transfection efficiency and cytotoxicity of PEI/DNA formulations are highly dependent on the molecular weight of PEI, e.g., PEI (5 K) was reported to have lower cytotoxicity and show DNA transfection efficiency comparable to PEI (25K)in vitro.One rational way was suggested to combine low molecular weight PEIs together using degradable links to form combined PEIs with suitable high molecular weights. It was expected that the toxicity should be reduced, and the longterm safety should be improved because those combined PEIs should be degraded to much less toxic low molecular weight PEIs after delivering DNA into cells; meanwhile, those combined PEIs should have good transfection efficiency for gene delivery for the high enough molecular weights.Polysaccharides derived from plants have emerged as an important class of bioactive substances. Many medicinal and therapeutic properties are attributed to plant-derived polysaccharides. They were shown to modulate the immune system, have hypoglycemic, anti-thrombotic, antibiotic, anti-tumor and antiviral activities, lower blood pressure and the concentration of blood lipids, inhibit inflammation and microbial action, etc.In this paper, we report novel structurally well-defined LMW linear PEI-g-Polysaccharide copolymers for in vitro gene transfer. These copolymers were designed on the basis of the following reasons: (i) LMW PEI has a lower toxicity than HMW PEI,(ii) Polysaccharide reduces toxicity and meanwhile improves their gene transfection efficiency of the polymer/DNA complexes.
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