Jungwoo Oh

Suppression of hepatitis C virus replication by protein kinase C-related kinase 2 inhibitors that block phosphorylation of viral RNA polymerase.

Summary.u2002 Hepatitis C virus (HCV) infection is a serious threat to human health worldwide. In spite of the continued search for specific and effective anti‐HCV therapies, the rapid emergence of drug‐resistance variants has been hampering the development of anti‐HCV drugs designed to target viral enzymes. Targeting host factors has therefore emerged as an alternative strategy offering the potential to circumvent the ever‐present complication of drug resistance. We previously identified protein kinase C‐related kinase 2 (PRK2) as a cellular kinase that phosphorylates the HCV RNA‐dependent RNA polymerase (RdRp). Here, we report the anti‐HCV activity of HA1077, also known as fasudil, and Y27632, which blocks HCV RdRp phosphorylation by suppressing PRK2 activation. Treatment of a Huh7 cell line, stably expressing a genotype 1b HCV subgenomic replicon RNA, with 20u2003μm each of HA1077 and Y27632 reduced the HCV RNA level by 55% and 30%, respectively. A combination of the inhibitors with 100 IU/mL interferon α (IFN‐α) significantly potentiated the anti‐HCV drug activities resulting in approximately a 2‐log10 viral RNA reduction. We also found that IFN‐α does not activate PRK2 as well as its upstream kinase PDK1 in HCV‐replicating cells. Furthermore, treatment of HCV‐infected cells with 20u2003μm each of HA1077 and Y27632 reduced the levels of intracellular viral RNA by 70% and 92%, respectively. Taken together, the results identify PRK2 inhibitors as potential antiviral drugs that act by suppressing HCV replication via inhibition of viral RNA polymerase phosphorylation.

Interference of hepatitis C virus replication in cell culture by antisense peptide nucleic acids targeting the X-RNA

Summary.u2002 The RNA‐dependent RNA polymerase (RdRp) of hepatitis C virus (HCV) is the essential catalytic enzyme for viral genome replication. It initiates minus‐strand RNA synthesis from a highly conserved 98‐nt sequence, called the X‐RNA, at the 3′‐end of the plus‐strand viral genome. In this study, we evaluated the antiviral effects of peptide nucleic acids (PNAs) targeting the X‐RNA. Our in vitro RdRp assay results showed that PNAs targeting the three major stem‐loop (SL) domains of X‐RNA can inhibit RNA synthesis initiation. Delivery of X‐RNA‐targeted PNAs by fusing the PNAs to cell‐penetrating peptides (CPPs) into HCV‐replicating cells effectively suppressed HCV replication. Electrophoretic mobility shift assays revealed that the PNA targeting the SL3 region at the 5′‐end of X‐RNA dissociated the viral RdRp from the X‐RNA. Furthermore, delivery of the SL3‐targeted PNA into HCV‐infected cells resulted in the suppression of HCV RNA replication without activation of interferon β expression. Collectively, our results indicate that the HCV X‐RNA can be effectively targeted by CPP‐fused PNAs to block RNA–protein and/or RNA–RNA interactions essential for viral RNA replication and identify X‐RNA SL3 as an RdRp binding site crucial for HCV replication. In addition, the ability to inhibit RNA synthesis initiation by targeting HCV X‐RNA using antisense PNAs suggests their promising therapeutic potential against HCV infection.

Normally-Off GaN-on-Si MISFET Using PECVD SiON Gate Dielectric

We have developed a silicon oxynitride (SiON) deposition process using a plasma-enhanced chemical vapor deposition system for the gate dielectric of GaN-on-Si metal–insulator–semiconductor field-effect transistors (MISFETs). The optimized SiON film had a relative dielectric constant of 5.3 and a breakdown field of 12MV/cm. A normally-off GaN-on-Si MISFET fabricated with a 33-nm SiON gate dielectric exhibited a threshold voltage of ~2 V, an ON-resistance of <inline-formula> <tex-math notation=LaTeX>

Three-Dimensional Flexible All-Organic Conductors for Multifunctional Wearable Applications

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AlGaN/GaN-on-Si power FET with Mo/Au gate

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Highly Elastic and Conductive N-Doped Monolithic Graphene Aerogels for Multifunctional Applications

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Epitaxial ZnO gate dielectrics deposited by RF sputter for AlGaN/GaN metal-oxide-semiconductor high-electron-mobility transistors

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Evaluation of titanium disilicide/copper Schottky gate for AlGaN/GaN high electron mobility transistors

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SF6 plasma treatment for leakage current reduction of AlGaN/GaN heterojunction field-effect transistors

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The impact of gate to drain spacing on hot-carrier degradation in sub-100 nm Ni–Pt salicidation FinFETs

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