Abstrakt
The pharmacological mediator of RNAi, short interfering RNA (siRNA) showed great therapeutic potential, but still facing significant obstacles in reaching- its target site and effectively exerting -its silencing activity. Therefore, their use in clinical practice is limited due to disadvantages, such as inefficient cellular delivery, unfavourable immunogenic response, and restricted targeting specific cell types.
In this paper we report an example of strategy how to solve these problems. Our approach is based on design effective trans-membrane transporters using on the multifunctional, multitargeting principles.
This project utilize specific design for siRNA carries, developed on combination of the guanidine group (selective for phosphate, phosphodiester linkage) covalently connected with a number of hydrophobic building blocks, including steroids and oligopyrrolic macrocycles. These conjugates as results of overall structure and binding efficacy have a selectivity for complexing siRNA.
Primary examples of developed novel carries for efficient transmembrane siRNA transport are guanidine steroids and guanidine-substituted oligopyrrolic macrocycles. We have studied by spectroscopic tools dynamic complex formation of carriersiRNA and also their transport efficacy using PAMPA model.