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The search for an effective nonviral gene therapy vector has revealed several significant hurdles, such as transient expression and cytotoxicity, that impede the success of these systems. A terpolymer of poly(lysine-g-(lactide-b-ethylene glycol)) [pK-g-p(LL-b-EG)] has been developed, which is capable of stably packaging DNA with significantly less polycation than unmodified polylysine (pK) systems. A comparison of unmodified pK (DP=14, M(w)=2930) to pK grafted with p(LL-b-EG) (M(w tot)=7500) showed that the minimum amine/phosphate ratio (N:P(min)) needed for complete DNA condensation was reduced by 50%. However, when the molecular weight of pK was reduced (DP=4, M(w)=838), there was evidence of terpolymer interference with DNA condensation. Increasing the number of grafted p(LL-b-EG) chains produced a similar result of incomplete DNA condensation. All terpolymer formulations produced complexes with DNA that had greater resistance to salt-induced dissociation and short-term exchange with excess DNA. Terpolymer-DNA complexes exhibited approximately zero-order plasmid release profiles over a period of 6 weeks. The rate of release was dependent on the complex N:P ratio as well as the molecular weights of pLL and pK. The ability to use terpolymer composition to control complex stability and controlled release can provide a means for system optimization for sustained expression profiles of exogenous DNA.


Susan Park, Kevin E Healy. Compositional regulation of poly(lysine-g-(lactide-b-ethylene glycol))-DNA complexation and stability. Journal of controlled release : official journal of the Controlled Release Society. 2004 Mar 24;95(3):639-51

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PMID: 15023473

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