In this review, a new concept called "Programmed Packaging" is proposed for developing non-viral gene delivery systems. A Multifunctional Envelope-type Nano Device (MEND) was developed based on this concept, which can enter into cells via macropinocytosis and facilitate transfection activities as efficiently as an adenovirus. Intracellular trafficking of MEND was optimized in order to prevent lysosomal degradation and to enhance nuclear translocation. A quantitative analytical method (CIDIQ) was also established to evaluate each step in intracellular trafficking of genes as well as carriers. A comparative study between Lipofectamin and an adenovirus showed that intra-nuclear disposition, which includes the transcriptional process, translational process, etc., can be the limiting step for Lipofectamin PLUS. These studies indicated the importance of controlling intra-nuclear disposition in the development of an efficient non-viral gene delivery system.