A new liposome system containing spermidine-condensed DNA and negative cone-forming lipids designed to improve gene delivery and expression is described. The compacted nature of condensed DNA forms permitted a higher extent of encapsulation of DNA in liposomes. These vesicles contained fusogenic cone-shaped lipids to increase fusion between liposomes and membranes to enhance the amount of DNA delivery into the cells. In addition, the insensitivity of condensed DNA forms to endonucleases and restriction enzymes, as well as their higher activity in both replication and transcription, improve foreign DNA expression. These improvements in condensed DNA encapsulation in liposomes, transfer into the cells, and DNA expression increase the number of transfected cells and produce a higher level of gene expression in most transfected cells. This is reflected in the 60-fold cell culture transfection increase compared with traditional liposome transfection systems. This liposome system does not cause any apparent damage to the transfected cells; furthermore, the liposomes are small, 400-500 nm, and have negative surface charges that can prolong their circulation half-lives in vivo, permitting their use for in vivo gene therapy applications.