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Abstract
RNA interference (RNAi) is a normal cellular process in which small RNAs control gene expression. siRNAs introduced into cells suppress gene expression through their recognition and cleavage of cognate mRNAs in a sequence specific manner. Due to its highly specific mode of action, RNAi has recently been tested for treatment or prevention of various diseases including organ transplantation as well as basic biomedical research. However, to achieve clinical success, there are some important issues that should be fully validated. First, siRNAs should be properly designed to avoid off-target effects. Second, siRNAs must be modified so as not to induce innate immune responses. Third, selective delivery of siRNA into desired organs or tissues is required. Despite such prerequisites, siRNAs are thought to be superior to traditional small molecule drug in terms of new drug development. In addition, in case of heart and islet transplantation which probably requires preservation of organs or cultivation of tissues for a while, siRNAs can be added to preserving solution or medium to control target gene expression during this period. In many research studies, mediators of innate immune response, inflammation, and cell death have been tested for alleviation of tissue injury and immune rejection after transplantation as potent targets of RNAi. We suggest that elucidation of exact mechanisms for tissue injury and immune rejection and subsequent selection and validation of target of RNAi in future studies might be helpful in enabling RNAi-based therapy in clinical organ transplantation to become a reality.
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Table 1.
실험동물 장기이식 모델에서의 RNA간섭치료 연구
Abbreviations: MyD88, myeloid differentiation factor 88; TRIF, TIR-domain-containing adapter-inducing interferon-; CCR5, CC-motif chemokine receptor 5; TNF-a, tumor necrosis factor-alpha; C3, complement 3; ETaR, endothelin A receptor; SHARP-2, split- and hairy-related protein-2; RelB, Rel/nuclear factor kappaB; 2m, 2-microglobulin.
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