ABSTRACT

Gene therapy is a medical strategy based on the delivery of genes as therapeutic agents for the correction of a mutation, prevention, or treatment of pathology. Numerous non-viral mediated gene delivery systems based cationic polymers have been developed to overcome safety issues related to viral vectors. The elaboration of smart polyplexes based on bioresponsive polymers, highly efficient and compatible showed a great promises and interest, in application for gene delivery. Genes delivery based pH-responsive polymers involves mainly distinct mechanisms. The first mechanism which is a protonation/deprotonation event, lean on the variation of acidic conditions between the normal physiological environment pH 7.4 and those of endosome and lysosome which drop to 5.5 and 4.5, respectively. The second mechanism is based on the destabilization or degradation of a pH-sensitive linker, which conjugates to the carrier and the cargo. The acid-labile linkage is a moiety added to polymeric chain which will be hydrolyzed as soon as it is in contact of acidic pH.