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Dive into the research topics where Sujeong Kim is active.

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Featured researches published by Sujeong Kim.


Molecular Therapy | 2011

Retroviral Gene Therapy for X-linked Chronic Granulomatous Disease: Results From Phase I/II Trial

Hyoung Jin Kang; Cynthia C. Bartholomae; Anna Paruzynski; Anne Arens; Sujeong Kim; Seung Shin Yu; Youngtae Hong; Chang Wan Joo; Nam Kyung Yoon; Jung Woo Rhim; Joong Gon Kim; Christof von Kalle; Manfred Schmidt; Sunyoung Kim; Hyo Seop Ahn

X-linked chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by a defect in the gp91(phox) gene. In an effort to treat X-CGD, we investigated the safety and efficacy of gene therapy using a retroviral vector, MT-gp91. Two X-CGD patients received autologous CD34(+) cells transduced with MT-gp91 after a conditioning regimen consisting of fludarabine and busulfan. The level of gene-marked cells was highest at day 21 (8.3 and 11.7% in peripheral blood cells) but decreased to 0.08 and 0.5%, respectively, 3 years after gene transfer. The level of functionally corrected cells, as determined by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase assay, reached a peak at day 17 (6.5% patient 1 (P1) and 14.3% patient 2 (P2) of total granulocytes) and declined to 0.05% (P1) and 0.21% (P2), 3 years later. Some retroviral vectors were found to have integrated within or close to the proto-oncogenes MDS1-EVI1, PRDM16, and CCND2; however, no abnormal cell expansion or related hematological malignancy was observed. Overall, the gene transfer procedure did not produce any serious adverse effects and was able to convert a significant fraction of blood cells to biologically functional cells, albeit for a short period of time.


International Journal of Cancer | 2010

The growth of brain tumors can be suppressed by multiple transplantation of mesenchymal stem cells expressing cytosine deaminase

Da-Young Chang; Seung-Wan Yoo; Youngtae Hong; Sujeong Kim; Se Joong Kim; Sung-Hwa Yoon; Kyung-Gi Cho; Sun Ha Paek; Young-Don Lee; Sung-Soo Kim; Haeyoung Suh-Kim

Suicide genes have recently emerged as an attractive alternative therapy for the treatment of various types of intractable cancers. The efficacy of suicide gene therapy relies on efficient gene delivery to target tissues and the localized concentration of final gene products. Here, we showed a potential ex vivo therapy that used mesenchymal stem cells (MSCs) as cellular vehicles to deliver a bacterial suicide gene, cytosine deaminase (CD) to brain tumors. MSCs were engineered to produce CD enzymes at various levels using different promoters. When co‐cultured, CD‐expressing MSCs had a bystander, anti‐cancer effect on neighboring C6 glioma cells in proportion to the levels of CD enzymes that could convert a nontoxic prodrug, 5‐fluorocytosine (5‐FC) into cytotoxic 5‐fluorouracil (5‐FU) in vitro. Consistent with the in vitro results, for early stage brain tumors induced by intracranial inoculation of C6 cells, transplantation of CD‐expressing MSCs reduced tumor mass in proportion to 5‐FC dosages. However, for later stage, established tumors, a single treatment was insufficient, but only multiple transplantations were able to successfully repress tumor growth. Our findings indicate that the level of total CD enzyme activity is a critical parameter that is likely to affect the clinical efficacy for CD gene therapy. Our results also highlight the potential advantages of autograftable MSCs compared with other types of allogeneic stem cells for the treatment of recurrent glioblastomas through repetitive treatments.


Human Gene Therapy | 2011

Acquisition of HIV-1 resistance in T lymphocytes using an ACA-specific E. coli mRNA interferase.

Hideto Chono; Kazuya Matsumoto; Hiroshi Tsuda; Naoki Saito; Karim Lee; Sujeong Kim; Hiroaki Shibata; Naohide Ageyama; Keiji Terao; Yasuhiro Yasutomi; Junichi Mineno; Sunyoung Kim; Masayori Inouye; Ikunoshin Kato

Transcriptional activation of gene expression directed by the long terminal repeat (LTR) of HIV-1 requires both the transactivation response element (TAR) and Tat protein. HIV-1 mutants lacking a functional tat gene are not able to proliferate. Here we take a genetic approach to suppress HIV-1 replication based on Tat-dependent production of MazF, an ACA-specific endoribonuclease (mRNA interferase) from Escherichia coli. When induced, MazF is known to cause Bak- and NBK-dependent apoptotic cell death in mammalian cells. We first constructed a retroviral vector, in which the mazF (ACA-less) gene was inserted under the control of the HIV-1 LTR, which was then transduced into CD4+ T-lymphoid CEM-SS cells in such a way that, upon HIV-1 infection, the mazF gene is induced to destroy the infecting HIV-1 mRNA, preventing HIV-1 replication. Indeed, when the transduced cells were infected with HIV-1 IIIB, the viral replication was effectively inhibited, as HIV-1 IIIB p24 could not be detected in the culture medium. Consistently, not only cell growth but also the CD4 level was not affected by the infection. These results suggest that the HIV-1-LTR-regulated mazF gene was effectively induced upon HIV-1 IIIB infection, which is sufficient enough to destroy the viral mRNA from the infected HIV-1 IIIB to completely block viral proliferation in the cells, but not to affect normal cell growth. These results indicate that the T cells transduced with the HIV-1-LTR-regulated mazF gene acquire HIV-1 resistance, providing an intriguing potential for the use of the HIV-1-LTR-regulated mazF gene in anti-HIV gene therapy.


Gene Therapy | 2003

Construction of a retroviral vector production system with the minimum possibility of a homologous recombination

Seung Shin Yu; Eunyoung Han; Youngtae Hong; J.R. Lee; Sujeong Kim; Sunyoung Kim

A recombination between the short homologous regions of nucleotide sequences in the retroviral vector and packaging cell line has been thought to be a major cause of the production of replication-competent retrovirus (RCR). Therefore, the removal of overlapping sequences between the vector and the packaging constructs is crucial for minimizing the possibility of homologous recombination, and therefore, the production of RCR. We have recently constructed a series of retroviral vectors that contain no viral coding sequences, but still produce high viral titer and high-level gene expression. However, many previously constructed murine leukemia viurs (MLV)-based packaging constructs contained significantly long 5′ and/or 3′ untranslated regions of MLV, which are also present in the retroviral vector, and as such could possibly lead to homologous recombination. To make a retroviral production system that is free from homologous recombination, we constructed expression plasmids for gag-pol and env, precisely starting from the start codon and ending at the stop codon of respective open reading frames. When the packaging function was provided from one plasmid, a vector containing bits of all three viral coding sequences produced RCR at a significant frequency, while our vector remained free of any RCR. Our retrovirus production system is anticipated to have the minimum possible frequency of RCR production due to the elimination of potential sites for homologous recombination. Based on these results, a highly efficient new packaging line Vamp that contains no overlapping sequences with our retroviral vector was also developed.


Journal of Gene Medicine | 2004

Factors affecting retrovirus-mediated gene transfer to human CD34+ cells.

Youngtae Hong; Karim Lee; Seung Shin Yu; Sujeong Kim; Kim Jm; Hee Young Shin; Sunyoung Kim

Retrovirus‐mediated gene transfer is a useful technology in studying the biology of hematopoietic stem cells (HSCs) as well as in developing gene therapy products for a variety of human diseases. One of the most important factors determining the success of these studies is the number of HSCs receiving the gene of interest.


Biochemical and Biophysical Research Communications | 2011

Improvement of biological and pharmacokinetic features of human interleukin-11 by site-directed mutagenesis.

Yuni Jung; Haesook Ahn; Dong-Sik Kim; Yu Ri Hwang; Seong-Hyun Ho; Jong-Mook Kim; Sujeong Kim; Suyong Ma; Sunyoung Kim

Recombinant human interleukin-11 (rhIL-11) has been shown to increase platelet counts in animals and humans and is the only drug approved for its use in chemotherapy-induced thrombocytopenia (CIT). However, due to its serious side effects, its clinical use has been limited. The current work presents significantly improved efficacy of rhIL-11 via knowledge based re-designing process. The interleukin-11 mutein (mIL-11) was found to endure chemical and proteolytic stresses, while retaining the biological activity of rhIL-11. The improved efficacy of mIL-11 was evident after subcutaneous administration of mIL-11 and rhIL-11 in the rodent and primate models. More than three-fold increase in maximum plasma concentration (Cmax) and area-under-the curve (AUC) was observed. Furthermore, three-fold higher increase in the platelet counts was obtained after seven consecutive daily subcutaneous mIL-11 injections than that with rhIL-11. The mIL-11 demonstrated not only improved stability but also enhanced efficacy over the currently used rhIL-11 regimen, thereby suggesting less toxicity.


AIDS Research and Human Retroviruses | 1999

Sequences downstream of the RNA initiation site of the HTLV type I long terminal repeat are sufficient for trans-activation by human cytomegalovirus immediate-early proteins.

Jong-Mook Kim; Youngtae Hong; Sujeong Kim; Myung-Hwan Cho; Mitsuaki Yoshida; Kuan-Teh Jeang; William Burns; Sunyoung Kim

Human T cell leukemia virus type I infection is associated with a low incidence of morbidity in the form of adult T cell leukemia and neurologic disease, suggesting that there are other factors determining the pathogenic outcome of infection. We found that HCMV could infect various human cell lines known to be susceptible to HTLV-I infection, including T cell lines already harboring HTLV-I, and that HCMV infection could highly activate gene expression from the HTLV-I LTR. In addition, the coexpression of IE1 and IE2 genes of HCMV increased transcription from the HTLV-I LTR. The deletion analysis indicated that the entire U3 region is not required, but that the 216-bp region from +101 to +316 is sufficient for activation of the LTR by IE1 and IE2. These results suggest that HCMV IE proteins may affect the level of HTLV-I gene expression in coinfected individuals by interacting with HTLV-I LTR sequences.


Journal of Gene Medicine | 2008

Development of an in vitro cell culture assay system for measuring the activation of a neighbouring gene by the retroviral vector.

Youngtae Hong; Seung Shin Yu; Nam-Kyung Yoon; Sung June Kang; J.R. Lee; Sujeong Kim; Jong-Mook Kim; Karim Lee; Jiwon Jang; Sunyoung Kim

The use of retroviral vectors has shown an actual clinical benefit in a few inherited diseases. However, the occurrence of cases of leukemia after the X‐SCID gene therapy trial raised concerns about the safety of insertional mutagenesis inherent to the biology of the retrovirus. Although the retrovirus has long been known to integrate into the host chromosome, and thus have the potential to activate the nearby gene, there has been no convenient method of studying or assaying such a cis‐activation phenomenon.


Molecular Therapy | 2005

104. Stable High Level Gene Expression by Minimum Sized Murine Leukemia Virus (MLV)-Based Retroviral Vectors in the Mouse Model

Seung Shin Yu; Youngtae Hong; Sujeong Kim; Chang Wan Joo; Nam Kyung Yoon; Sunyoung Kim

Top of pageAbstract Despite the frequent use of MLV-based retroviral vectors in gene therapy trials, there have been three major criticisms, often relative to the lentivirus-based retroviral vector. First is the claim that MLV-based vector drives a lower level and shorter period gene expression in vivo. However, there is no firm basis for this claim as there have been no serious comparative experiments done thus far between two retroviral vectors. Second, MLV-based vectors cannot deliver a gene to the resting cells. Although this currently holds true, considering the given speed of progress in cell biological technique, the number of cell type to which MLV-based vector can deliver the gene would increase. Third is the possibility of insertional mutagenesis. However, it should not be considered any disadvantage over lentiviral vector, because it also integrates into the host genome like any other retroviruses. Contrary to what has been perceived in the community, MLV-based vectors still have distinctive advantages over lentiviral vectors, especially when the easiness of overall handling, including the production process, is concerned. To study how MLV-based vectors perform in vivo, we tested a series of vectors derived from MT in mouse model. MT is a minimum sized vector that contains no viral coding sequences, but can efficiently drive gene expression and produce high viral titer (Kim et al, J. Virol, 1998, 994-1004; Yu et al, J. Virol. 2000, 8775-8780; Gene Ther., 2000, 797-804; Hong et al, J. Gen. Med., 2003, 18-29). Bone marrow (BM) cells were isolated from mice, and Lin- cells were enriched and transduced with MT-based vectors expressing GFP. 1 |[times]|105 Lin- cells were pre-stimulated with a specially formulated medium for 48 hours and transduced three times at MOI=5 over the period of another two days. At the end, 50|[ndash]|60% of these BM-derived cells became positive to GFP. Immediately after the gene delivery procedure, 1|[times]|106 cells were injected into the lethally irradiated recipient mice through the tail vein (i.v.) or the BM directly (i.BM). During the 40 weeks of follow-up analysis, some differences were found between i.v. (14|[sim]|23%) and i.BM (5|[sim]|14%) injections in terms of the percentage of GFP+ cells in PB cells. Our in vivo comparative analysis indicated that the vector containing the MSCV LTR gave a higher GFP expression than the one with the MoMuLV LTR. Similar long term gene expression was also observed in the mouse model using a MoMuLV-LTR driven vector expressing gp91 (whose defect leads to chronic granulomatous disease in humans). When the integration sites of MT-based vector were analyzed in transduced cells, it appears that there is no strong preference for any particular site as expected from the previous reports. Our data indicated that MLV-based vectors can drive high level gene expression during a substantially long period of time. Given the fact that an MLV-based vector is the most scrutinized gene delivery vehicle with a proven record of safety and efficiency, it should remain a strong candidate as a gene transfer system in the actual clinical settings.


Molecular Therapy | 2004

396. Factors Affecting Retroviral Gene Transfer to Human CD34+ Cells

Youngtae Hong; Seung-Shin Yu; Sujeong Kim; Kim Jm; Sunyoung Kim

Retrovirus-mediated gene transfer is a useful technology in studying the biology of hematopoietic stem cells (HSCs) as well as in developing gene therapy products for a variety of human diseases. One of the most important factors determining the success of these studies is the number of HSCs receiving the gene of interest. We tested various parameters for their influences on gene transfer efficiency to CD34+ cells derived from bone marrow. Based on literature survey, three medium formulations of CD34+ cells have been compared for their effects on gene delivery efficiency and differentiation of them. We also tested whether FBS that used in medium formulation, could be replaced with human serum or synthetic material. Formulation A, consisting of stem cell factor, Flt-3 ligand, thrombopoietin, and IL-3, provided optimum results in that it maintained the highest percentage of CD34+ cells during the culture as well as produced the highest gene delivery efficiency. It was found that the synthetic serum substitute containing bovine serum albumin, insulin and human transferrin could replace the fetal bovine serum present in original formulation A without compromising gene transfer efficiency. When the transduction procedure was repeated three times, the gene could be delivered in up to 60% of the cell population. Gene delivery efficiency was comparable between CD34+ cells derived from bone marrow and mobilized peripheral blood. Our data could be useful in designing the procedure for stem cell gene therapy and providing a basis for further improving the conditions for gene transfer to various HSCs.

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Sunyoung Kim

Seoul National University

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Jong-Mook Kim

Seoul National University

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Seung Shin Yu

Seoul National University

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Youngtae Hong

Seoul National University

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Seong-Hyun Ho

Seoul National University

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Woong Hahn

Seoul National University

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Dong-Sik Kim

Seoul National University

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Karim Lee

Seoul National University

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J.R. Lee

Seoul National University

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Jae-Gyun Jeong

Seoul National University

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