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Dive into the research topics where Yuan-Chuan Chen is active.

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Featured researches published by Yuan-Chuan Chen.


IEEE Transactions on Electron Devices | 1995

Comparison of GaInP/GaAs heterostructure-emitter bipolar transistors and heterojunction bipolar transistors

Yue-Fei Yang; C.C. Hsu; E. S. Yang; Yuan-Chuan Chen

Carbon-doped GaInP/GaAs heterojunction bipolar transistors (HBTs) and heterostructure-emitter bipolar transistors (HEBTs) grown by MOCVD were fabricated. Experimental comparison of HBTs and HEBTs has been made based on the dc and the RF performance. HBTs have higher current gains than those of HEBTs in the high current regime, while HEBTs offer a smaller offset voltage and better uniformity in dc characteristics across the wafer. The current gain and cutoff frequency of the DEBT with a 150 /spl Aring/ emitter set-back layer are comparable to those of HBTs. DC (differential) current gains of 600 (900) and 560 (900) were obtained at a collector current density of 2.5/spl times/10/sup 4/ A/cm/sup 2/ for the HBT and HEBT, respectively. The cutoff frequencies are 37 and 31 GHz for the HBT and HEBT, respectively. It is shown that there is negligible contribution of the diffusion capacitance to the emitter capacitance in HEBTs with a thin emitter set-back layer but not with a thick emitter set-back layer. The behavior of HEBTs both in dc and RF characteristics is similar to that of HBTs. >


Molecular Therapy | 2013

Inhibition of Hepatitis B Virus Gene Expression and Replication by Ribonuclease P

Chuan Xia; Yuan-Chuan Chen; Hao Gong; Wenbo Zeng; Gia-Phong Vu; Phong Trang; Sangwei Lu; Jianguo Wu; Fenyong Liu

Nucleic acid-based gene interfering approaches, such as those mediated by RNA interference and RNase P-associated external guide sequence (EGS), have emerged as promising antiviral strategies. The RNase P-based technology is unique, because a custom-designed EGS can bind to any complementary mRNA sequence and recruit intracellular RNase P for specific degradation of the target mRNA. In this study, a functional EGS was constructed to target hepatitis B virus (HBV) essential transcripts. Furthermore, an attenuated Salmonella strain was constructed and used for delivery of anti-HBV EGS in cells and in mice. Substantial reduction in the levels of HBV gene expression and viral DNA was detected in cells treated with the Salmonella vector carrying the functional EGS construct. Furthermore, oral inoculation of Salmonella carrying the EGS construct led to an inhibition of ~95% in the levels of HBV gene expression and a reduction of ~200,000-fold in viral DNA level in the livers and sera of the treated mice transfected with a HBV plasmid. Our results suggest that EGSs are effective in inhibiting HBV replication in cultured cells and mammalian livers, and demonstrate the use of Salmonella-mediated delivery of EGS as a promising therapeutic approach for human diseases including HBV infection.


Proceedings of the National Academy of Sciences of the United States of America | 2012

Effective inhibition of cytomegalovirus infection by external guide sequences in mice

Xiaohong Jiang; Hao Gong; Yuan-Chuan Chen; Gia-Phong Vu; Phong Trang; Chen-Yu Zhang; Sangwei Lu; Fenyong Liu

Ribonuclease P complexed with external guide sequence (EGS) bound to mRNA represents a unique nucleic acid-based gene interference approach for modulation of gene expression. Compared with other strategies, such as RNA interference, the EGS-based technology is unique because a custom-designed EGS molecule can hybridize with any mRNA and recruit intracellular ribonuclease P for specific degradation of the target mRNA. It has not been reported whether the EGS-based technology can modulate gene expression in mice. In this study, a functional EGS was constructed to target the mRNA encoding the protease (mPR) of murine cytomegalovirus (MCMV), which is essential for viral replication. Furthermore, a unique attenuated strain of Salmonella was generated for gene delivery of EGS in cultured cells and in mice. Efficient expression of EGS was observed in cultured cells treated with the generated Salmonella vector carrying constructs with the EGS expression cassette. Moreover, a significant reduction in mPR expression and viral growth was found in MCMV-infected cells treated with Salmonella carrying the construct with the functional EGS sequence. When MCMV-infected mice were orally treated with Salmonella carrying EGS expression cassettes, viral gene expression and growth in various organs of these animals were reduced and animal survival improved. Our study suggests that EGS RNAs, when expressed following Salmonella-mediated gene transfer, effectively inhibit viral gene expression and infection in mice. Furthermore, these results demonstrate the feasibility of developing Salmonella-mediated delivery of EGS as a unique approach for treatment that reduces viral diseases in vivo.


PLOS Pathogens | 2012

A Hsp40 Chaperone Protein Interacts with and Modulates the Cellular Distribution of the Primase Protein of Human Cytomegalovirus

Yonggang Pei; Wenmin Fu; Ed Yang; Ao Shen; Yuan-Chuan Chen; Hao Gong; Jun Chen; Jun Huang; Gengfu Xiao; Fenyong Liu

Genomic DNA replication is a universal and essential process for all herpesvirus including human cytomegalovirus (HCMV). HCMV UL70 protein, which is believed to encode the primase activity of the viral DNA replication machinery and is highly conserved among herpesviruses, needs to be localized in the nucleus, the site of viral DNA synthesis. No host factors that facilitate the nuclear import of UL70 have been reported. In this study, we provided the first direct evidence that UL70 specifically interacts with a highly conserved and ubiquitously expressed member of the heat shock protein Hsp40/DNAJ family, DNAJB6, which is expressed as two isoforms, a and b, as a result of alternative splicing. The interaction of UL70 with a common region of DNAJB6a and b was identified by both a two hybrid screen in yeast and coimmunoprecipitation in human cells. In transfected cells, UL70 was primarily co-localized with DNAJB6a in the nuclei and with DNAJB6b in the cytoplasm, respectively. The nuclear import of UL70 was increased in cells in which DNAJB6a was up-regulated or DNAJB6b was down-regulated, and was reduced in cells in which DNAJB6a was down-regulated or DNAJB6b was up-regulated. Furthermore, the level of viral DNA synthesis and progeny production was increased in cells in which DNAJB6a was up-regulated or DNAJB6b was down-regulated, and was reduced in cells in which DNAJB6a was down-regulated or DNAJB6b was up-regulated. Thus, DNAJB6a and b appear to enhance the nuclear import and cytoplasmic accumulation of UL70, respectively. Our results also suggest that the relative expression levels of DNAJB6 isoforms may play a key role in regulating the cellular localization of UL70, leading to modulation of HCMV DNA synthesis and lytic infection.


Journal of Virology | 2011

Human Cytomegalovirus Primase UL70 Specifically Interacts with Cellular Factor Snapin

Ao Shen; Ji Lei; Edward Z. Yang; Yonggang Pei; Yuan-Chuan Chen; Hao Gong; Gengfu Xiao; Fenyong Liu

ABSTRACT Genomic DNA synthesis is a universally conserved process for all herpesviruses, including human cytomegalovirus (HCMV). HCMV UL70 is believed to encode the primase of the DNA replication machinery, a function which requires localization in the nucleus, the site of viral DNA synthesis. No host factors that interact with UL70 have been reported. In this study, we provide the first direct evidence that UL70 specifically interacts with Snapin, a human protein that is predominantly localized in the cytoplasm and is associated with cellular vesicles. The interaction between UL70 and Snapin was identified in both the two-hybrid screen in yeast and coimmunoprecipitation in human cells. The nuclear import of UL70 was decreased in cells overexpressing Snapin and increased in cells in which the expression of Snapin was downregulated with anti-Snapin small interfering RNA (siRNA) molecules, respectively. Furthermore, viral DNA synthesis and progeny production were decreased in cells overexpressing Snapin and increased in the anti-Snapin siRNA-treated cells, respectively. In contrast, no significant difference in the nuclear level of UL70, viral DNA synthesis, and progeny production was found among the parental cells and cells that either expressed a control empty vector or were treated with control siRNA molecules that did not recognize any viral or cellular transcripts. Our results suggest that Snapin may play a key role in regulating the cellular localization of UL70 in HCMV, leading to modulation of viral DNA synthesis and progeny production.


PLOS ONE | 2012

Effective inhibition of human immunodeficiency virus 1 replication by engineered RNase P ribozyme.

Wenbo Zeng; Yuan-Chuan Chen; Yong Bai; Phong Trang; Gia-Phong Vu; Sangwei Lu; Jianguo Wu; Fenyong Liu

Using an in vitro selection procedure, we have previously isolated RNase P ribozyme variants that efficiently cleave an mRNA sequence in vitro. In this study, a variant was used to target the HIV RNA sequence in the tat region. The variant cleaved the tat RNA sequence in vitro about 20 times more efficiently than the wild type ribozyme. Our results provide the first direct evidence that combined mutations at nucleotide 83 and 340 of RNase P catalytic RNA from Escherichia coli (G83 -> U83 and G340 -> A340) increase the overall efficiency of the ribozyme in cleaving an HIV RNA sequence. Moreover, the variant is more effective in reducing HIV-1 p24 expression and intracellular viral RNA level in cells than the wild type ribozyme. A reduction of about 90% in viral RNA level and a reduction of 150 fold in viral growth were observed in cells that expressed the variant, while a reduction of less than 10% was observed in cells that either did not express the ribozyme or produced a catalytically inactive ribozyme mutant. Thus, engineered ribozyme variants are effective in inhibiting HIV infection. These results also demonstrate the potential of engineering RNase P ribozymes for anti-HIV application.


Viruses | 2014

Engineered RNase P Ribozymes Effectively Inhibit Human Cytomegalovirus Gene Expression and Replication

Zhu Yang; Gia-Phong Vu; Hua Qian; Yuan-Chuan Chen; Yu Wang; Michael Reeves; Ke Zen; Fenyong Liu

RNase P ribozyme can be engineered to be a sequence-specific gene-targeting agent with promising application in both basic research and clinical settings. By using an in vitro selection system, we have previously generated RNase P ribozyme variants that have better catalytic activity in cleaving an mRNA sequence than the wild type ribozyme. In this study, one of the variants was used to target the mRNA encoding human cytomegalovirus (HCMV) essential transcription factor immediate-early protein 2 (IE2). The variant was able to cleave IE2 mRNA in vitro 50-fold better than the wild type ribozyme. A reduction of about 98% in IE2 expression and a reduction of 3500-fold in viral production was observed in HCMV-infected cells expressing the variant compared to a 75% reduction in IE2 expression and a 100-fold reduction in viral production in cells expressing the ribozyme derived from the wild type sequence. These results suggest that ribozyme variants that are selected to be highly active in vitro are also more effective in inhibiting the expression of their targets in cultured cells. Our study demonstrates that RNase P ribozyme variants are efficient in reducing HCMV gene expression and growth and are potentially useful for anti-viral therapeutic application.


PLOS ONE | 2013

Engineered External Guide Sequences Are Highly Effective in Inhibiting Gene Expression and Replication of Hepatitis B Virus in Cultured Cells

Zhigang Zhang; Gia-Phong Vu; Hao Gong; Chuan Xia; Yuan-Chuan Chen; Fenyong Liu; Jianguo Wu; Sangwei Lu

External guide sequences (EGSs) are RNA molecules that consist of a sequence complementary to a target mRNA and recruit intracellular ribonuclease P (RNase P), a tRNA processing enzyme, for specific degradation of the target mRNA. We have previously used an in vitro selection procedure to generate EGS variants that efficiently induce human RNase P to cleave a target mRNA in vitro. In this study, we constructed EGSs from a variant to target the overlapping region of the S mRNA, pre-S/L mRNA, and pregenomic RNA (pgRNA) of hepatitis B virus (HBV), which are essential for viral replication and infection. The EGS variant was about 50-fold more efficient in inducing human RNase P to cleave the mRNA in vitro than the EGS derived from a natural tRNA. Following Salmonella -mediated gene delivery, the EGSs were expressed in cultured HBV-carrying cells. A reduction of about 97% and 75% in the level of HBV RNAs and proteins and an inhibition of about 6,000- and 130-fold in the levels of capsid-associated HBV DNA were observed in cells treated with Salmonella vectors carrying the expression cassette for the variant and the tRNA-derived EGS, respectively. Our study provides direct evidence that the EGS variant is more effective in blocking HBV gene expression and DNA replication than the tRNA-derived EGS. Furthermore, these results demonstrate the feasibility of developing Salmonella -mediated gene delivery of highly active EGS RNA variants as a novel approach for gene-targeting applications such as anti-HBV therapy.


RNA Biology | 2012

Ribonuclease P-mediated inhibition of human cytomegalovirus gene expression and replication induced by engineered external guide sequences

Xiaohong Jiang; Yuan-Chuan Chen; Hao Gong; Phong Trang; Sangwei Lu; Fenyong Liu

External guide sequences (EGSs) are RNA molecules that can bind to a target mRNA and direct ribonuclease P (RNase P), a tRNA processing enzyme, for specific cleavage of the target mRNA. Using an in vitro selection procedure, we have previously generated EGS variants that efficiently direct human RNase P to cleave a target mRNA in vitro. In this study, we constructed EGSs from a variant to target the overlapping region of the mRNAs coding for human cytomegalovirus (HCMV) capsid scaffolding protein (CSP) and assemblin, which are essential for viral capsid formation. The EGS variant was about 40-fold more active in directing human RNase P to cleave the mRNA in vitro than the EGS derived from a natural tRNA. Moreover, a reduction of about 98% and 75% in CSP/assemblin gene expression and a reduction of 7000- and 250-fold in viral growth were observed in HCMV-infected cells that expressed the variant and the tRNA-derived EGS, respectively. Our study shows that the EGS variant is more effective in blocking HCMV gene expression and growth than the tRNA-derived EGS. Moreover, these results demonstrate the utility of highly active EGS RNA variants in gene targeting applications including anti-HCMV therapy.


BioMed Research International | 2013

RNase P-Associated External Guide Sequence Effectively Reduces the Expression of Human CC-Chemokine Receptor 5 and Inhibits the Infection of Human Immunodeficiency Virus 1

Wenbo Zeng; Gia-Phong Vu; Yong Bai; Yuan-Chuan Chen; Phong Trang; Sangwei Lu; Gengfu Xiao; Fenyong Liu

External guide sequences (EGSs) represent a new class of RNA-based gene-targeting agents, consist of a sequence complementary to a target mRNA, and render the target RNA susceptible to degradation by ribonuclease P (RNase P). In this study, EGSs were constructed to target the mRNA encoding human CC-chemokine receptor 5 (CCR5), one of the primary coreceptors for HIV. An EGS RNA, C1, efficiently directed human RNase P to cleave the CCR5 mRNA sequence in vitro. A reduction of about 70% in the expression level of both CCR5 mRNA and protein and an inhibition of more than 50-fold in HIV (R5 strain Ba-L) p24 production were observed in cells that expressed C1. In comparison, a reduction of about 10% in the expression of CCR5 and viral growth was found in cells that either did not express the EGS or produced a “disabled” EGS which carried nucleotide mutations that precluded RNase P recognition. Furthermore, the same C1-expressing cells that were protected from R5 strain Ba-L retained susceptibility to X4 strain IIIB, which uses CXCR4 as the coreceptor instead of CCR5, suggesting that the RNase P-mediated cleavage induced by the EGS is specific for the target CCR5 but not the closely related CXCR4. Our results provide direct evidence that EGS RNAs against CCR5 are effective and specific in blocking HIV infection and growth. These results also demonstrate the feasibility to develop highly effective EGSs for anti-HIV therapy.

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Fenyong Liu

University of California

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Gia-Phong Vu

University of California

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Hao Gong

University of California

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Phong Trang

University of California

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Sangwei Lu

University of California

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Gengfu Xiao

Chinese Academy of Sciences

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Ao Shen

University of California

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Xiaohong Jiang

University of California

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Yong Bai

University of California

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