Abstract
The concept of drug delivery system (DDS) was born approximately 30 years ago and developed in many aspects such as controlled release, absorption enhancement and targeting. New aspect in DDS is required for gene therapy with highly controlled delivery system especially to control the intracellular trafficking of carrier as well as DNA. Multi-functional carrier system will he required to overcome the barriers such as plasma membrane, endosomal membrane and nuclear membrane. Receptor-mediated endocytosis is one of the most selective and efficient entrance pathway for gene delivery, however, endosomal escape is then a critical barrier for efficient cytosolic delivery. pH-sensitive liposome is able to deliver encapsulated macromolecules into cytosol depending on the decreased endosomal pH. Active targeting to nuclear compartment is essential, otherwise DNA will be degraded in cytosol. Nuclear localization signals have been identified and used for nuclear delivery of macromolecules including DNA. For the rational optimization of the carrier system for gene delivery, quantitative assay of DNA in each organella should be critical. New method in measuring the amount of DNA in nucleus has been established using PCR amplification method. This method can be applied to measure intracellular amount of DNA in other organella, which leads to optimize the intracellular trafficking of DNA with artificial carrier and to surpass the efficiency of virus.
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