RNA interfetence (RNAi) mechanism as a basis for future successful treatment of chronic hepatitis B infection

  • Ana Nikolova University "Goce Delcev" - Stip, Macedonia
  • Darko Bosnakovski University "Goce Delcev" - Stip, Macedonia



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.




Author Biography

Ana Nikolova, University "Goce Delcev" - Stip, Macedonia


Born :06.10.1991

Adress :‘Jajce” 23 , Shtip . R.Macedonia

Home Tel: +389 32613 146; Cell Phone: +389 77 832 881

E-mail: anikolova56@yahoo.comana_nikolova@hotmail.com



EDUCATION: I started High School in 2006 in the Medical High School “Jane Sandanski” in Shtip, R. Macedonia as a Pharmacy Assistant. And I finish it in June, 2010.  In September, 2010 I started as a Student on the University of “Goce Delcev “ Shtip, R. Macedonia on the Faculty for Pharmacy.

In March, 2013 I was awarded with ERASMUS Scholarship and went to Medical University in Sofia,R. Bulgaria on the Faculty for Pharmacy. I was on 5 months education and upgrade my knowlens in pharmaceutical technology, clinical biochemistry and pharmaceutical chemistry. After five months I came back. Now I am making a research for RNAi which is called “ Modern therapy based on RNAi ( I researched the RNAi threatment for  HBV chronic infection).  I finished my master study.



2014 -  Praktikant in the Clinic Center – Shtip , R. Macedonia 3  months as a pharmacy technician  in  Hospital Pharmacy.

2015 May - Experience in holding a lecture and presentation of the Faculty of Pharmacy - University Goce Delcev for new therapeutics that are based on RNAi mechanism. While dealing with research on RNAi therapeutics.

SKILLS: Fluent speak  of English

Fluent speak of  German language .

I have pass B1 level, German language.

Microsoft Office Word / Excel and Power Point work



Scholarship for talented and excellent students from the Ministry of Education, Government of  R. Macedonia from 2011/2012 – 2014/2015 .

ERASMUS Certificate for succesfull completed ERASMUS   Program In R. Bulgaria , 2013

Certificate for participation on 1st Erasmus International Week – Encountering Erasmus + Sharing Erasmus Experience , 2013

Certificate for succesfull completer Basic comunication, negotiation skills and work ethics –from USAID , 2009


PERSONAL: communicative, hard working and ambitious. Flexible to work with great enthusiasm for science.