Journal of Antivirals & Antiretrovirals
Open Access
ISSN: 1948-5964
+44 1300 500008
ISSN: 1948-5964
+44 1300 500008
Andres Merits
Scientific Tracks Abstracts: JAA
Background: Antisense technology is one of the most straightforward approaches for suppressing unwanted gene expression. It can be applied as a treatment for the largest variety of disorders including cancer and infectious diseases. Various modifi cations of deoxyribose/ribose sugar backbone have greatly improved the effi ciency, bioavailability and increased in vivo halflife of these compounds. Method: Our technology is based on oligonucleotide analogs that contain specifi cally modifi ed DNA bases and that are bound to organic complexes with highly selective nuclease activity. Th e structure of such compounds has been optimized using computer predictions, cell culture and in vivo activity assays. Results: Two LNA-gapmer oligonucleotides, targeting genomic RNA of hepatitis C virus (HCV), were selected. Th ese compounds contained three modifi ed nucleobases (either 5-OH-dC or 8-oxo-dG) and had eff ective concentration 50 in HCV replicon cell line assay in low nanomolar range. Th ey were equally effi cient against the parental HCV-1b replicons and the replicons, containing mutations (T54A or T54S+A156S in NS3) associated with resistance against protease inhibitors. Th e catalytic activity of the compounds conjugated with artifi cial nuclease leaded to the further lowering of the eff ective concentration of the compounds. Importantly, the compounds were also highly active in mice model where a single dose (5 microgram/kg) of compound resulted in ca 50% reduction of targeted marker gene expression. Conclusions: Th e oligonucleotides with nucleobase modifi cations are much more potent antiviral inhibitors than oligonucleotides without such modifi cations. Acknowledgements: Th e compounds were developed in collaboration with BTD Ltd (Tallinn, Estonia), the research was supported by grant from the Estonian Enterprises.
Andres Merits has completed his Ph.D at the age of 26 years from Moscow State University (Russia) and postdoctoral studies from Institute of Biotechnology, University of Helsinki (Finland). He is group leader of RNA virus studies and the professor of Applied virology in Institute of Technology, University of Tartu. The main areas of research include molecular biology of RNA viruses (alphaviruses and HCV), development of systems and tools of virus-based bio- and gene technology and novel antiviral compounds. He has published more than prereviewed 50 papers in reputed journals.