NOVEL VECTORS FOR GENE DELIVERY FORMED BY SELF-ASSEMBLY OF DNA WITH POLY(L-LYSINE) GRAFTED WITH HYDROPHILIC POLYMERS

Complexes formed between DNA and cationic polymers are attracting incr easing attention as novel synthetic vectors for delivery of genes. We are trying to improve biological properties of such complexes by orien ted self-assembly of DNA with cationic-hydrophilic block copolymers, d esigned to enshroud the complex within a protective hydrophilic polyme r corona. Poly(L-lysing) (pLL) grafted with range of hydrophilic polym er blocks, including poly(ethylene glycol) (pEG), dextran and poly[N-( 2-hydroxypropyl)methacrylamide] (pHPMA), shows efficient binding to DN A and mediates particle self-assembly and inhibition of ethidium bromi de/DNA fluorescence. The complexes formed are discrete and typically a bout 100 nm diameter, viewed by atomic force microscopy. Surface charg es are slightly shielded by the presence of he hydrophilic polymer, an d complexes generally show decreased cytotoxicity compared with simple pLL/DNA complexes. pEG-containing complexes show increased transfecti on activity against cells in vitro. Complexes formed with all polymer conjugates showed greater aqueous solubility than simple pLL/DNA compl exes, particularly at charge neutrality. These materials appear to hav e the ability to regulate the physicochemical and biological propertie s of polycation/DNA complexes, and should find important applications in packaging of nucleic acids for specific biological applications. (C ) 1998 Elsevier Science B.V.