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Omschrijving

Small interfering RNA molecules offer a promising tool for the treatment of various diseases including cancer and a number of other inherent or acquired disorders, due to their ability to knockdown essentially any target gene of interest. However, the lack of appropriate delivery systems limits the novel and encouraging therapeutic and clinical potential of siRNA. As optimization of the delivery strategy remains one of the major restrictions for clinical use, research has progressively focused on the development of synthetic delivery devices suitable for safe and specific delivery of siRNA to the target site. The main focus of this thesis was the discovery and optimization of novel polymers as highly effective and biocompatible siRNA delivery systems. On this occasion various polymers were developed featuring reduced toxicity, improved biodegradability and enhanced endosomolytic properties in order to overcome the major bottlenecks for siRNA delivery. Finally, pre-programmed bioresponsive carriers were realized, which act more dynamically in response to their cellular microenvironment representing a considerably step in the optimization process for nucleic acid delivery.