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Featured researches published by Seung Shin Yu.


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.


Journal of Gene Medicine | 2004

Electrotransfer of human IL-1Ra into skeletal muscles reduces the incidence of murine collagen-induced arthritis

Jae-Gyun Jeong; Jong-Mook Kim; Seong-Hyun Ho; Woong Hahn; Seung Shin Yu; Sunyoung Kim

It has previously been demonstrated that high levels of gene expression in skeletal muscles can be achieved after direct in vivo electrotransfer of naked plasmid DNA. The purpose of this study is to examine the potential of in vivo electroporation of plasmid DNA encoding human IL‐1Ra for the prevention of murine collagen‐induced arthritis (CIA).


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 Virology | 2000

The 17 Nucleotides Downstream from the env Gene Stop Codon Are Important for Murine Leukemia Virus Packaging

Seung Shin Yu; Jong-Mook Kim; Sunyoung Kim

ABSTRACT We have identified a previously unknown nucleotide sequence important for the packaging of murine leukemia virus. This nucleotide sequence is located downstream from the stop codon of theenv gene but does not overlap the polypurine tract. Deletion of 17 bp from this region resulted in a more than 10-fold decrease in viral titer. Consistent with this result, the deletion mutant showed a 20- to 30-fold drop in the amount of virion RNA in the culture supernatant. The total amount of virion protein in the culture supernatant was comparable for the deletion mutant and the parental virus, suggesting that the mutant construct could release the empty viral particles. These results suggested that the packaging signal sequence might be present at the two extreme sites of the viral genome, one in the region around the splice donor sequence downstream from the 5′ long terminal repeat (LTR) and the other immediately upstream from the 3′ LTR. Implications for gene therapy, especially in regard to construction of retroviral vectors and packaging constructs, are discussed.


Journal of General Virology | 1996

Essential role of NF-kappa B in transactivation of the human immunodeficiency virus long terminal repeat by the human cytomegalovirus 1E1 protein.

Sunyoung Kim; Seung Shin Yu; Vic Narry Kim

The 72 kDa 1E1 protein of human cytomegalovirus (HCMV) is one of a few viral regulatory proteins expressed immediately after infection of a host cell. Although it is now well-established that 1E1 is a potent transcriptional activator of the human immunodeficiency virus (HIV) long terminal repeat (LTR), the identity of the nucleotide sequence responsive to 1E1 remains elusive and the molecular mechanism of this interaction is not well-understood. We have constructed various LTR mutants and tested them for their ability to be activated by 1E1 using transient transfection assays. Mutations in the NF-kappa B sites, of either a few changes in the nucleotide sequence or a deletion of the entire region, abrogated 1E1-driven transactivation. Deletion of the Tat-responsive element (TAR) had no significant effect on reporter expression. Mutations in the Sp1 sites or the TATA box significantly lowered LTR activity, but this is probably due to an effect on the general transcription system, as these elements are also required for the transactivation of the LTR by many stimulators including Tat, tumour necrosis factor alpha (TNF-alpha). E1A/E1B and phorbol myristate acetate (PMA). In addition, gel retardation analysis demonstrated that NF- kappa B activity was significantly increased in human T lymphoid H9 and monocytic U937 cell lines constitutively expressing 1E1. Taken together, these data suggest that NF- kappa B plays a central role in the 1E1 transactivation of the HIV LTR.


Journal of Gene Medicine | 2003

Construction of a high efficiency retroviral vector for gene therapy of Hunter's syndrome

Youngtae Hong; Seung Shin Yu; Jong Mook Kim; Karim Lee; Young Soon Na; Chester B. Whitley; Yoshikazu Sugimoto; Sunyoung Kim

As an alternative method to the conventional therapies for Hunters syndrome, which is a lethal lysosomal storage disorder, we have developed gene delivery vehicles using a series of retroviral vectors. The objective of this study was to develop a safe and efficient retroviral vector and to optimize conditions for efficient transduction of human bone marrow CD34+ stem cells using our vector.


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.


International Journal of Hematology | 2002

High efficiency gene transfer to human CD34+ cells

Youngtae Hong; Karim Lee; Ji Young Choi; Seung Shin Yu; Eunok Kim; Yoshikazu Sugimoto; M. Ueno; Ikunoshin Kato; Sun-Whe Kim

We have previously reported the development of improved MLV-based retroviral vectors whose prototype is entitled MT (Kim et al, J. Virol. 72:994–1044; Yu et al, Gene Therapy 7:797–804). The MT vector does not contain any viral coding sequences, and thus the possibility of homologous recombination between the vector and the packaging genome is virtually nil. Indeed, in a shotgun RCR detection assay, an MT-based vector did not produce any RCR. On the contrary, the MFG vector, containing parts of all three viral coding sequences (gag, pol, and env), generated a significant number of RCR. In addition to being safe, MT-based vectors produce levels of gene expression and viral titer comparable to or higher than other vectors currently available within the community. Based on this vector, we have constructed a number of retroviral vectors that can be used for the treatment of a variety of human diseases. Our major target diseases are those that can be treated with or the status of which can be significantly improved with bone marrow transplantation. To obtain the most significant therapeutic effects, it is necessary to achieve the highest possible gene delivery efficiency, drive the highest level of gene expression, and prevent expression of the inserted therapeutic gene from being negatively influenced by the genome environment. To these ends, we compared various LTRs for their effects on the level of gene expression, tested the effect of cisacting elements that may influence chromatin structure or position effect of the inserted gene, and studied different transduction conditions for their gene delivery efficiency. Data recently obtained from these experiments will be presented. *** DIRECT SUPPORT *** A00RC002 00014


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.


Journal of Clinical Oncology | 2010

A phase II clinical study of interleukin-11 mutein to treat patients with chemotherapy-induced thrombocytopenia.

Y. Jung; Seong-Hyun Ho; Seung Shin Yu; S. Wu; Y. Zhang; L. Xu; Y. Dai; Y. Teng; S. Ma; S. Song

9113 Background: To demonstrate the safety and efficacy of genetically engineered human interleukin-11 mutein (mIL-11) on chemotherapy- induced thrombocytopenia (CIT) patients, a multicenter random...

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Sunyoung Kim

Seoul National University

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Sujeong Kim

Seoul National University

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Jong-Mook Kim

Seoul National University

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Youngtae Hong

Seoul National University

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Karim Lee

Seoul National University

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Seong-Hyun Ho

Seoul National University

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Jae-Gyun Jeong

Seoul National University

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J.R. Lee

Seoul National University

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