RNA interfetence (RNAi) mechanism as a basis for future successful treatment of chronic hepatitis B infection
RNAi - RNA interference is a regulatory mechanism which is found in most eukaryotic and prokaryotic cells. This mechanism can directly cause blockage of gene activity through double stranded siRNAs homologous sequences. Edru Fire and Craig Mello's discovery of RNAi in the 90s refers to the presence of double stranded micro molecules within the eukaryotic cells named siRNAs. The RNAi mechanism is led by basic dsRNA. In the cytoplasm, this dsRNA is recognized by Dicer protein, through which dsRNa is transfered into smaller micro siRNAs carrying the main inhibitory role. Furthermore, this siRNAs, found within the RISC system, with the participation of Ago2 enzymes associates with the previously recognized target iRNA and blocks the activity of their genes. Pharmaceutical companies are developing strategies for the formulation of therapeutics that have the basis of a RNAi mechanism.
About 360 million of the Earth's population are infected with chronic hepatitis B virus. Due to its high specificity and risk of death, numerous in vitro and in vivo clinical methods are researched to find out possibilities of treatment for the chronic hepatitis B with RNAi.
According to this, the main purpose of this project would be to thoroughly examine the molecular way of RNAi, as well as to explore the opportunities for its therapeutic application in chronic hepatitis B.
With the investigated in vitro and in vivo RNAi studies in chronic hepatitis B, it is perceived that the success of the treatment requires a combination of siRNA or shRNA sequences. In order to achieve a greater efficiency, reliability and duration of treatment, it is eminently important to develop an appropriate distributive pattern of these micro molecules to the liver cells. Studies of Arrowhead Research Corporation and Nucleonics Biotechnology confirm that the treatment based on RNAi for chronic hepatitis successfully allows a virus reduction in serum.
From the research we can deduce that the general reduction of the virus is performed with suppression of the genes which are responsible for DNA replication, as well as suppression of the genes which are responsible for encoding HbsAg and HbeAg. If these therapies are used appropriately with the prescribed therapeutic doses, the effect will be visible after a month-long therapy and with long-lasting effect. RNAi therapeutics are expected to appear on the market in 2018.
Keywords: RNA interference (RNAi), siRNAs, chronic hepatitis B virus, gene- therapy, DPC delivery model, LNP delivery model.