C형 간염 백신 개발의 전망

성영철 대한간학회 1997 Clinical and Molecular Hepatology(대한간학회지) Vol.3 No.2

Overview-Cancer Vaccine

Sung, Young Chul 가톨릭대학교 가톨릭암센터 2006 암심포지움 Vol.- No.1

In Vivo Kinetics and Biodistribution of HB-110, a Novel HBV DNA Vaccine, after Administration in Mice

Eun Sung Kang,Chae Young Kim,Seon Beom Kim,임세진,Se Hwan Yang,성영철,Byong Moon Kim 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.3

This study investigated the pharmacokinetic profile and biodistribution of HB-110, a novel HBV therapeutic vaccine candidate, in mice. HB-110 was rapidly degraded in the blood after i.v. injection with a half-life of 1.9±0.083 min, and was no longer detected at 60 min except in one individual near the detection limit. In the i.m. injection, plasmid DNA was detectable at the injection site until 11 days after administration, but the amounts were just above the detection limit. The blood concentration of HB-110 showed a maximum of 604 pg/mL at 15 min after i.m. injection, which was followed by degradation to undetectable levels at 90 min. The plasmid DNA in tissues peaked at 90 min after administration. The highest concentration of plasmid DNA was detected in the liver (24.172 pg/mg tissue), and considerable amounts were also observed in the lung (9.467 pg/mg tissue) and spleen (7.688 pg/mg tissue). The amount of plasmid DNA in tissues was 2 to 3 orders of magnitude lower than in the injection site at the same time points. The HB-110 concentration in tissues, including gonads, decreased rapidly and was undetectable 24 h after administration.

RawPEACH: Multiband CSMA/CA-Based Cognitive Radio Networks

정조운,성영철,Dan Keun Sung 한국통신학회 2009 Journal of communications and networks Vol.11 No.2

A new medium access control (MAC) scheme embedding physical channels into multiband carrier sense multiple access/ collision avoidance (CSMA/CA) networks is proposed to provide strict quality of service (QoS) guarantee to high priority users. In the proposed scheme, two priority classes of users, primary and secondary users, are supported. For primary users physical channels are provided to ensure strict QoS, whereas secondary users are provided with best-effort service using CSMA/CA modified for multiband operation. The performance of the proposed MAC scheme is investigated using a new multiband CSMA/CA Markov chain model capturing the primary user activity and the operation of secondary users in multiple bands. The throughput of secondary users is obtained as a function of the primary user activity and other CSMA/CA parameters. It is shown that the new MAC scheme yields larger throughput than the conventional single-band CSMA/CA when both schemes use the same bandwidth.

Purification and Characterization of the cynR Regulatory Protein from a High Level Expression System

김영숙,장준,성영철,Kim, Young-Sug,Chang, Jun,Sung, Young-Chul Korean Society for Biochemistry and Molecular Biol 1991 한국생화학회지 Vol.24 No.4

cynR 조절 단백질은 T7 RNA polymerase/T7 promoter계에 의해 선택적으로 형질발현이 가능하였으며, 이로부터 DEAE-cellulose, phosphocellulose, 그리고 Sephadex G-200 컬럼 크로마토그래피를 이용함으로써 분리, 정제되었다. 분리된 cynR 조절 단백질은 그 분자량이 64,000 달톤으로, 두 개의 동일한 subunit으로 구성되어 있음이 확인되었고, 실제 N 말단의 아미노산 서열은 cynR 유전자의 염기서열로부터 예측한 것과 일치하였다. Gel retardation 실험을 통해 cynR 조절 단백질과 DNA의 특이적 결합을 조사한 결과, cynR 단백질은 cyn TSX operon과 cynR 유전자 사이의 짧은 intergenic region내의 영역에 특이적으로 결합하는 것이 밝혀졌다. The cynR protein, which is a positive regulator for cynTSX operon in the presence of cyanate as well as a negative regulator for its own gene, was overexpressed by the T7 RNA polymerase/T7 promoter expression system in which the cynR gene was cloned under the control of T7 promoter. The cynR protein was purified on the serial columns of DEAE-cellulose, phosphocellulose, and Sephadex G-200. Throughout the purification, the cynR protein was identified as a single band of 32,000 daltons on SDS-polyacrylamide gel. The molecular weight of the protein in the native state was determined to be 64,000 daltons by HPLC, suggesting that the cynR protein exists as a dimer. The N-terminal acid sequence of the purified cynR protein was essentially the same as those deduced from the DNA sequence of cynR gene. In the gel retardation assay, the regulatory protein was specifically bound to the intergenic region between the cynTSX operon and the cynR gene. This result suggests that cynR protein binds to the intergenic region and regulates the expression of cynTSX structural genes and cynR regulatory gene simultaneously.

과발현된 cycR 조절 단백질의 분리정제 및 그 특성

김영숙,장준,성영철 ( Young Sug Kim,Jun Chang,Young Chul Sung ) 생화학분자생물학회 1991 BMB Reports Vol.24 No.4

The cynR protein, which is a positive regulator for cynTSX operon in the presence of cyanate as well as a negative regulator for its own gene, was overexpressed by the T7 RNA polymerase/T7 promoter expression system in which the cynR gene was cloned under the control of T7 promoter. The cynR protein was purified on the serial columns of DEAE-cellulose, phosphocellulose, and Sephadex G-200. Throughout the purification, the cynR protein was identified as a single band of 32,000 daltons on SDS-polyacrylamide gel. The molecular weight of the protein in the native state was determined to be 64,000 daltons by HPLC, suggesting that the cynR protein exists as a dimer. The N-terminal acid sequence of the purified cynR protein was essentially the same as those deduced from the DNA sequence of cynR gene. In the gel retardation assay, the regulatory protein was specifically bound to the intergenic region between the cynTSX operon and the cynR gene. This result suggests that cynR protein binds to the intergenic region and regulates the expression of cynTSX structural genes and cynR regulatory gene simultaneously.

Human Immunodeficiency Virus Type 1의 Rev-Responsive Element의 기능 분석

이형열,이안휘,강신성,성영철,Lee, Hyeong-Yeol,Lee, Ann-Hwee,Kang, Shin-Sung,Sung, Young-Chul 생화학분자생물학회 1992 한국생화학회지 Vol.25 No.3

Human immunodeficiency virus type 1(HIV-1)의 Rev 단백질은 자신의 복제에 필수적으로 작용하는 조절단백질이다. 이 단백질은 구조유전자 mRNA를 핵에서 세포질로의 수송을 촉진함으로서 구조단백질의 발현을 유도하는 것으로 생각된다. 이러한 Rev 단백질은 HIV-1 RNA의 env 유전자 내에 존재하는 cis-acting element인 Rev responsive element(RRE)와 직접 결합함으로써 그 기능을 나타낸다. 컴퓨터 분석결과 RRE는 복잡한 RNA 이차구조 즉 하나의 central stem (I')과 작은 stem(I), 그리고 5개의 stem/loop들로(II, III, IV, V, VI) 구성되는 것으로 예견 되어졌다. 본 연구에서는 RRE RNA내의 어느 영역이 Rev 조절단백질의 반응에 필수적으로 작용하는가를 알아보기 위하여 RRE RNA내의 안정한 이차구조를 in vitro mutagenesis시켜 Rev 단백질과 RRE RNA mutants와의 상호작용을 p24 ELISA, reverse transcriptase assay, CAT assay 등의 방법으로 살펴보았다. 그 결과 RRE의 복잡한 이차구조 내에서 stem/loop II의 이차구조가 Rev 단백질의 작용에 필수적임을 밝혔으며, 다른 영역의 이차구조들은 Rev 조절단백질과 stem/loop II와의 상호작용을 증가시킴을 관찰하였다. 또한, stem/loopII내의 stem에는 Rev 단백질과의 반응에 관련된 기능 외에 Rev 단백질이 없을 때 구조유전자의 발현을 억제하는 기능을 가진 부위, 즉 cis-acting repressive sequence(CRS)가 존재함을 확인하였다. Expression of the structural proteins of human immunodeficiency virus type (HIV-1) requires the Rev protein encoded by the rev open reading frame. Rev protein interacts with Rev-responsive element RRE located in the env region of the viral mRNA and seems to mediate the export of the incompletely spliced viral mRNA to the cytoplasm. RRE has a complex secondary structure which is composed of a central stem (I'), a small stem (I) and 5 stem/loops (II, III, IV, V, VI). To investigate which region of RRE is essential for the interaction with Rev protein, mutational analysis in RRE was carried out. We examined the nature of the mutated RRE in several assay systems, p24 ELISA assay, Reverse Transcriptase assay and CAT assay. Here we show that the secondary structure of stem/loop II region is critical for Rev response. Other structural components within RRE RNA seem to have only subsidiary roles. We also show that RRE appears to contain a negative sequence which hinders the expression of structural gene in the absence of the Rev protein.

Th17과 자가면역 관절염

조미라,허유정,박진실,이선영,성영철,김호연,Cho, Mi-La,Heo, Yu-Jung,Park, Jin-Sil,Lee, Seon-Yeong,Sung, Young-Chul,Kim, Ho-Youn 대한면역학회 2007 Immune Network Vol.7 No.1

Autoimmune arthritis, such as rheumatoid arthritis (RA), is a chronic inflammatory disorder that primarily affects the joints and then results in their progressive destruction. Effector Th cells have been classified as Th1 and Th2 subsets based on their cytokine expression profiles and immune regulatory function. Another subset of T cells termed Th17 was recendy discovered and known to selectively produce IL-17. Also, Th17 was shown to be generated by TGF${\beta}$ and IL-6 and maintained by IL-23. IL-17 is a proinflammatory cytokine that is considered to involve the development of various inflammatory autoimmune diseases such as RA, asthma, lupus, and allograft rejection. IL-17 is present in the sera, synovial fluids and synovial biopsies of most RA patient. IL-17 activates RA synovial fibroblasts to synthesize IL-6, IL-8 and VEGF via PI3K/Akt and NF-${\kappa}B$ dependent pathway. IL-17 increases IL-6 production, collagen destruction and collagen synthesis. In addition, it not only causes bone resorption but also increases osteoclastogenesis and fetal cartilage destruction. Inhibition of the IL-17 production may contribute a novel therapeutic approach along with potent anti-inflammatory effect and with less immunosuppressive effect on host defenses.

DNA 를 이용한 백신 및 치료

송만기(M . K . Song),성영철(Y . C . Sung),이창우(C . Y . Lee) 대한천식알레르기학회 2001 천식 및 알레르기 Vol.21 No.2

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Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation

Chae Young Kim,Eun Sung Kang,Seon Beom Kim,Han Eol Kim,Jae Hoon Choi,Dong Sop Lee,Se Jin Im,Se Hwan Yang,성영철,Byong Moon Kim,김병기 생화학분자생물학회 2008 Experimental and molecular medicine Vol.40 No.6

Pulse-induced permeabilization of cellular membranes, generally referred to as electroporation (EP), has been used for years as a tool to increase macromolecule uptake in tissues, including nucleic acids, for gene therapeutic applications, and this technique has been shown to result in improved immunogenicity. In this study, we assessed the utility of EP as a tool to improve the efficacy of HB-110, a novel therapeutic DNA vaccine against chronic hepatitis B, now in phase 1 of clinical study in South Korea. The potency of HB-110 in mice was shown to be improved by EP. The rapid onset of antigen expression and higher magnitude of humoral and cellular responses in electric pulse-treated mice revealed that EP may enable a substantial reduction in the dosage of DNA vaccine required to elicit a response similar in magnitude to that achievable via conventional administration. This study also showed that EP-based vaccination at 4-week-intervals elicited a cellular immune response which was about two-fold higher than the response elicited by conventional vaccination at 2-week intervals. These results may provide a rationale to reduce the clinical dose and increase the interval between the doses in the multidose vaccination schedule. Electric pulsing also elicited a more balanced immune response against four antigens expressed by HB-110: S, preS, Core, and Pol.