EFFICIENT GENE DELIVERY WITH NEUTRAL COMPLEXES OF LIPOSPERMINE AND THIOL-REACTIVE PHOSPHOLIPIDS

The presence of thiol-reactive phospholipid derivatives, such as N-4-( p-maleimidophenyl)butyryl) dipalmitoylphosphatidylethanolamine (MPB-DP PE), in electrically neutral lipospermine/DNA particles results in mor e than a 100-fold increased transfection efficiency of human hepatoma HepG2 cells and murine 3T3 fibroblasts. These effects could be ascribe d to the presence of thiol-reactive functions, such as maleimide, brom oacetamide and dithiopyridyl linkage, on the transfecting particles. W e propose that such particles react with thiol groups present at the s urface of the cells, leading to their covalent anchoring a process tha t is probably followed by an endocytosis of the complex. (C) 1995 Acad emic Press, Inc.