engleski

The great potential of RNA interference

RNA interference (RNAi) has recently became a powerful tool in biomedical research and drug development. It is an endogenously present regulatory mechanism of most eukaryote cells, discovered as a biological phenomenon only a decade ago. The basic principle of RNAi involves the destruction of messenger RNA (mRNA) upon interaction with homologous double stranded RNA (dsRNA), which is also known as small interfering RNA (siRNA). This mechanism has revolutionized approaches in determining gene functions and it has also shown great potential for therapeutic application. Different methods for delivering siRNA into cells have been developed. The exogenously introduced siRNA has been shown to utilize cellular machinery in the process of gene knockdown. The recognition protein DGCR8 (which is a dsRNA binding protein) and processing proteins like DROSHA, DICER or other homologues (which are RNaseIII ribonucleases) are a part of this machinery and normally present in eukaryote cells. In various model systems, nanoparticles have proved their efficiency in the process of delivering small interfering RNA into a cell. Once inside the cell, nanoparticles release the small interfering RNA in order for it to be accessible to the cellular machinery. Despite the excitement about this remarkable process there are number of problems that must be overcome prior to making RNAi a real therapeutic modality. These include improved and targeted delivery of siRNA into cells as well as a variety of off-target effects. Another problem that must be surmount is the fact that on-target effects of RNAi are transient in nature, particularly in rapidly dividing cells, and the suppressed phenotype is lost within approximately one week. Nevertheless, clinical trials that test RNAi therapeutics have already entered into the clinical phase. The objective of ongoing clinical trials is to replace existing treatment modalities (which are more toxic) and to create better tolerated and more effective therapeutics.

RNA interference; small interfering RNA; therapeutics

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