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연세대학교 오종원 교수님 연구실에서 파나진의 PNA를 이용하여 JEV 복제를 저해한 연구논문을 아래와 같이 발표하였습니다.
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Antiviral Res. 2009 Jun;82(3):122-33. Epub 2009 Feb 20.
Inhibition of Japanese encephalitis virus replication by peptide nucleic acids targeting cis-acting elements on the plus- and minus-strands of viral RNA.
Yoo JS, Kim CM, Kim JH, Kim JY, Oh JW.
Department of Biotechnology, Yonsei University, Shinchon-dong, Seodaemun-gu, Seoul, Republic of Korea.
Abstract
Japanese encephalitis virus (JEV) is a major cause of acute viral encephalitis in humans. The single-stranded, plus-sense viral genome, which is used for translation and minus-strand RNA synthesis, and its complementary minus-strand viral RNA contain various sequences and RNA secondary structures conserved in flaviviruses, providing potential targets for antisense agents. Here, we investigated the antiviral effects of peptide nucleic acids (PNAs) targeting cis-acting signals at the 5'-untranslated region (UTR), 3'-UTR, and genome cyclization motifs on the plus-strand RNA, as well as the 95-nucleotide 3'-end of the minus-strand RNA, which serves as a template for plus-strand RNA synthesis by the viral RNA-dependent RNA polymerase (RdRp). Among the tested cell-penetrating peptide (CPP)-PNA conjugates, a 17-mer PNA conjugate targeting the top of the 3'-UTR loop structure was most effective in suppressing virus proliferation. In vitro RdRp assays and electrophoretic mobility shift assays using a functional recombinant JEV RdRp showed that the 3'-terminal region-targeting PNAs could inhibit RNA synthesis by competing with viral RdRp for binding to a selected cis-acting element at the 3'-end of plus- and minus-strand viral RNAs. Collectively, our results suggest that CPP-PNA conjugates can suppress JEV proliferation by blocking RNA-protein or RNA-RNA interactions essential for productive viral infection.
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