DNA-POLYCATION NANOSPHERES AS NONVIRAL GENE DELIVERY VEHICLES

Nanospheres synthesized by salt-induced complex coacervation of cDNA a nd polycations such as gelatin and chitosan were evaluated as gene del ivery vehicles. DNA-nanospheres in the size range of 200-750 nm could transfect a variety of cell lines. Although the transfection efficienc y of the nanospheres was typically lower han that of lipofectamine and calcium phosphate controls in cell culture, the beta-gal expression i n muscle of BALB/c mice was higher and more sustained than that achiev ed by naked DNA and lipofectamine complexes. This gene delivery system has several attractive features: (1) ligands can be conjugated to the nanosphere for targeting or stimulating receptor-mediated endocytosis ; (2) lysosomolytic agents can be incorporated to reduce degradation o f the DNA in the endosomal and lysosomal compartments; (3) other bioac tive agents or multiple plasmids can be co-encapsulated; (4) bioavaila bility of the DNA can be improved because of protection from serum nuc lease degradation by the polymeric matrix; (5) the nanosphere can be l yophilized for storage without loss of bioactivity. (C) 1998 Elsevier Science B.V.