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RNA interference as a new tool in therapeutics

A discovery of RNA interference was a big turnover in molecular biology. Major advantage of RNA interference for therapeutic applications was that it utilizes cellular machinery that efficiently allows targeting of complementary transcripts resulting in down regulation of gene expression of virtually any gene. This is possible because RNA interference is a regulatory mechanism of most eukaryotic cells in the form of using double stranded RNA molecules to direct homology-dependent control of gene activity. Recognition protein DGCR8 which is a dsRNA binding protein and processing proteins like DROSHA, DICER or other homologues which are RNAaseIII ribonucleases, are needed for initial step of gene silencing and are normally present in eukaryotic cells and believed to be involved in defense against viruses. The basic principle of RNA interference involves destruction of mRNA upon interaction with homologous dsRNA. Studies have shown that both viral and non-viral siRNA delivery methods as like as delivery of chemically synthesized siRNAs to the cell can provide selective gene suppression. Despite the excitement about this remarkable process there are a number of hurdles and concerns that must be overcome prior to making RNAi a real therapeutic modality. These include off target effects and possibility to induce insertional mutagenesis and malignant transformation, as well as problems with using effective delivery methods to mediate gene silencing without causing toxicity. The use of siRNA as future therapeutics in human diseases require more rigorous investigation of the rules that govern its efficacy and selectivity, development of strategies to avoid side effects, and improvement of the delivery systems.

RNA interference; siRNA; therapeutics

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