The concept of molecular machinery is useful for design of stimuli-responsive gene delivery systems in the mammalian cell

Since the first generation of molecular machines including photoresponsive crown ethers and its analogues was reported by Shinkai et al., a huge number of molecular machines exhibiting dynamic chemical and physical functions have been designed and developed. On the other hand, non-viral vectors are desired to possess conflicting properties to associate with DNA until reaching the nucleus as their final destination and dissociate from DNA there. In other words, non-viral vectors should work as a sort of molecular machinery. To overcome this dilemma, recently, much attention is focused on the development of the intelligent vectors, also called as "stimuli responsive vectors' working as molecular machines. In this review, stimulus responsive gene delivery systems in which some structural factors and/or physiological properties are regulated in response to extracellular signals such as redox, pH, ultrasound, light, temperature, etc. are introduced as a new generation of non-viral vectors. These extracellular signals such as ultrasound, light, and temperature can be potent stimuli capable of site-, timing-, and duration-specific gene expression.