Inhibition of HCV replication

by vitro selected RNA aptamers

Prof. Seong-Wook Lee

Departmenr of Molecular Biology, Dankook University, Korea

2005. 4. 1

 

Characteristics of RNAs which can adopt complex structures to bind target proteins with high affinities and encode amplificable genetic information make RNA a potentially very useful diagnostic and/or therapeutic lead compounds. Such short RNA ligands, termed RNA aptamers, have been identified from a random RNA library to bind several proteins including non-RNA binding proteins with high affinity and specificity using in vitro selection techniques, called systemic evolution of ligands by exponential enrichment (SELEX). In the present study, we employed an RNA combinatorial library and isolated and characterized RNA aptamers for the HCV NS3 helicase domain and NS5B replicase essential for the HCV multiplication.

(I) RNA aptamers against HCV NS3 helicase domain:

(I) RNA aptamers against HCV NS5B replicase:

In conclusion, we isolated and characterized specific and avid RNA aptamers against regulatory proteins critical for HCV replication. Of note, intracellular expression of these RNAs efficiently inhibited HCV replicon replication. These results suggest that the RNA aptamers could be useful not only as therapeutic and diagnostic agents of HCV infection but also as a powerful tool for the study of HCV replication mechanism.

 

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Last update: April 1, 2005