• 제목/요약/키워드: Oligonucleotide-based molecules

검색결과 10건 처리시간 0.041초

Modulation of Immunosuppression by Oligonucleotide-Based Molecules and Small Molecules Targeting Myeloid-Derived Suppressor Cells

  • Lim, Jihyun;Lee, Aram;Lee, Hee Gu;Lim, Jong-Seok
    • Biomolecules & Therapeutics
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    • 제28권1호
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    • pp.1-17
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    • 2020
  • Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exert suppressive function on the immune response. MDSCs expand in tumor-bearing hosts or in the tumor microenvironment and suppress T cell responses via various mechanisms, whereas a reduction in their activities has been observed in autoimmune diseases or infections. It has been reported that the symptoms of various diseases, including malignant tumors, can be alleviated by targeting MDSCs. Moreover, MDSCs can contribute to patient resistance to therapy using immune checkpoint inhibitors. In line with these therapeutic approaches, diverse oligonucleotide-based molecules and small molecules have been evaluated for their therapeutic efficacy in several disease models via the modulation of MDSC activity. In the current review, MDSC-targeting oligonucleotides and small molecules are briefly summarized, and we highlight the immunomodulatory effects on MDSCs in a variety of disease models and the application of MDSC-targeting molecules for immuno-oncologic therapy.

Electrical Recognition of Label-Free Oligonucleotides upon Streptavidin-Modified Electrode Surfaces

  • Park, Jong-Wan;Jung, Ho-Sub;Lee, Hea-Yeon;Kawai, Tomoji
    • Biotechnology and Bioprocess Engineering:BBE
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    • 제10권6호
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    • pp.505-509
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    • 2005
  • For the purpose of developing a direct label-free electrochemical detection system, we have systematically investigated the electrochemical signatures of each step in the preparation procedure, from a bare gold electrode to the hybridization of label-free complementary DNA, for the streptavidin-modified electrode. For the purpose of this investigation, we obtained the following pertinent data; cyclic voltammogram measurements, electrochemical impedance spectra and square wave voltammogram measurements, in $Fe(CN)_6^{3-}/Fe(CN)_6^{4-}$ solution (which was utilized as the electron transfer redox mediator). The oligonucleotide molecules on the streptavidin-modified electrodes exhibited intrinsic redox activity in the ferrocyanide-mediated electrochemical measurements. Furthermore, the investigation of electrochemical electron transfer, according to the sequence of oligonucleotide molecules, was also undertaken. This work demonstrates that direct label-free oligonucleotide electrical recognition, based on biofunctional streptavidin-modified gold electrodes, could lead to the development of a new biosensor protocol for the expansion of rapid, cost-effective detection systems.

Therapeutic aptamers: developmental potential as anticancer drugs

  • Lee, Ji Won;Kim, Hyun Jung;Heo, Kyun
    • BMB Reports
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    • 제48권4호
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    • pp.234-237
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    • 2015
  • Aptamers, composed of single-stranded DNA or RNA oligonucleotides that interact with target molecules through a specific three-dimensional structure, are selected from pools of combinatorial oligonucleotide libraries. With their high specificity and affinity for target proteins, ease of synthesis and modification, and low immunogenicity and toxicity, aptamers are considered to be attractive molecules for development as anticancer therapeutics. Two aptamers - one targeting nucleolin and a second targeting CXCL12 - are currently undergoing clinical trials for treating cancer patients, and many more are under study. In this mini-review, we present the current clinical status of aptamers and aptamer-based cancer therapeutics. We also discuss advantages, limitations, and prospects for aptamers as cancer therapeutics. [BMB Reports 2015; 48(4): 234-237]

전극 기반의 전하 주입을 통한 DNA 전하수송 특성 측정 (Probe-based Charge Injection Study of DNA Charge Transfer for Applications to Molecular Electro-optic Switching)

  • 류호정;김희영;김동현
    • 전자공학회논문지SC
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    • 제48권3호
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    • pp.53-59
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    • 2011
  • 본 논문에서는 DNA 올리고뉴클리오타이드(oligonucleotide)를 통한 전하 이동을 기반으로 하는 분자성 전자광학 스위칭 소자를 제시한다. DNA 올리고머(oligomer)가 흡착되어 있는 금전극에 전자들이 주입되어 전극으로부터 DNA 올리고머로 전하가 흘러가게 하고 이 전하의 이동도를 광학적 스위칭으로 확인할 수 있도록 제안되었다. DNA 올리고머의 흡착량이 증가함에 따라 DNA를 통한 전하의 이동성과 전극 표면에서의 전하전달 제한성으로 인해 전리전류는 감소하였다. DNA의 끝단에 합성된 Cy3 형광 분자의 점멸도를 전극 기반의 전하 주입법을 이용하여 확인하였다. 이러한 결과들은 DNA 올리고머를 이용한 새로운 분자성 전자광학 스위칭 소자에 이용될 수 있다.

Nanoparticle-based Detection Technology for DNA Analysis

  • Park, Hyun-Gyu
    • Biotechnology and Bioprocess Engineering:BBE
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    • 제8권4호
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    • pp.221-226
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    • 2003
  • With the current rapid development of nanotechnology and synthesis technology for designed oligonucleotides or oligonucleotide-modified nanoparticle conjugates, the combined strategies have become one of the most valuable methods in detection technology for DNA analysis. Using the uniquely recognizable interactions of pre-designed DNA molecules in assembling nanoparticles, various novel approaches have been recently developed towards detecting specific DNA sequences. Here we describe the key fundamentals and issues of this promising strategies ranging from the initial findings of rationally designed DNA-based assembly of nanoparticles to the extended chip-based detection system. Some limitations of these new strategies and possible approaches will be also discussed for the practical application in the area of DNA microarray detection.

조직내교잡법을 이용한 결핵균의 검출 (Detection of Mycobacterium Tuberculosis by In Situ Hybridization)

  • 박창수;김영철;이지신;정종재;김두홍;김진
    • Tuberculosis and Respiratory Diseases
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    • 제48권5호
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    • pp.699-708
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    • 2000
  • 배경 : 올리고누클레오티드 탐식자를 이용한 조직내교잡법은 감염성 질환의 진단에 이용되고 있는 분자병리학적 검사방법이다. 그러나 결핵균의 세포벽에는 다량의 지방 성분이 포함되어 있어 탐식자의 침투에 어려움이 있다. 따라서 본 연구에서는 탐식자의 침투력을 높일 수 있는 조건을 알아보고, 결핵의 조직학적 진단법으로써 조직내교잡법의 이용 가능성을 확인해 보고자 한다. 방법 : 결핵으로 진단된 환자의 인체조직 절편과 배양된 결핵균을 흰쥐의 간 조직 내에 인위적으로 주입하여 제작한 실험조직 절편을 실험대상으로 하고, 바이오틴을 부착시킨 올리고누클레오티드 탐식자를 이용하여 조직내교잡법을 시행하였으며, 탐식자의 효과적인 침투를 위해 전처리를 시도하였다. 결과 : 펩신-염산 (2 mg/ml, 0.1M) 혼합액을 이용한 전처리 과정 (5-6분) 후 조직내교잡법을 수행한 결과 배양된 결핵균을 주입한 실험조직에서 결핵균의 검출에 성공할 수 있었다. 간 조직이 주사바늘에 의해 기계적으로 손상된 자리를 따라 군데군데 위치하고 있는 배양액 내에서 불규칙하게 모여있는 점상 혹은 간상의 양성반응을 관찰할 수 있었으며, 민감도는 80-90% 수준이었다. 그러나 결핵환자의 조직절편에서는 조직내교잡법을 이용하여 결핵균을 검출할 수 없었다. 결론 : 이는 배양액 내에서 빠르게 증식하는 결핵균과는 달리 인체에 감염된 결핵균에서는 rRNA의 양이 적어, 바이오틴이 부착된 탐식자를 이용한 조직내교잡법의 민감도를 벗어났을 것으로 추정된다. 따라서 향후 조직내교잡법으로 인체조직 내의 결핵균을 진단하기 위해서는 제자리 중합효소연쇄반응 (in situ PCR) 법의도입이나, 보다 높은 민감도를 갖는 동위원소를 부착 시킨 탐식자의 사용이 필요하다고 생각된다.

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Development of PCR-Based Screening Methods for Macrolide Type Polyketides in Actinomycetes

  • Hyun, Chang-Gu;Suh, Joo-Won
    • Journal of Applied Biological Chemistry
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    • 제42권3호
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    • pp.119-124
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    • 1999
  • About two thirds of the naturally occurring antibiotics have been discovered from actinomycetes. Therefore, the probability of discovering further new antibiotics from actinomycetes is declining as many known metabolites are isolated repeatedly. However, various efforts leave been made in order to enhance the probability of discovering novel compounds. In the present study, we have developed new screening strategies based on the antibiotic biosynthetic pathway, and the genetic information, utilizing polymerase chain reaction. We have selected macrolide type polyketides. In order to divide the ansamycin group antibotic of macrolide type polyketides, we have selected 3-amino-5-hydroxybenzoic acid (AHBA) moiety which contains a biosynthetically unique structural element in the group as a target molecules. Oligonucleotide primers were designed to amplify DNA fragments of macrolide type polyketide synthase and AHBA synthase genes from fourteen actinomycetes species. This method was successfully applied to all three of the known macrolide type polyketide produccing actinomycetes tested. In addition, it also identified the presence of potential macrolide type polyketide producing genes from seven actinomycetes that were known to produce none of macrolide type polyketides, and AHBA biosynthetic genes in one actinomycetes. This technique is potentially useful for the screening of new antibiotices and cloning of their biosynthetic genes.

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Electrochemical Detection of $17{\beta}-estradiol$ by using DNA Aptamer Immobilized Nanowell Gold Electrodes

  • Kim, Yeon-Seok;Jung, Ho-Sup;Lee, Hea-Yeon;Kawai, Tomoji;Gu, Man-Bock
    • 한국생물공학회:학술대회논문집
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    • 한국생물공학회 2005년도 생물공학의 동향(XVI)
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    • pp.88-92
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    • 2005
  • Aptamer is the single-stranded oligonucleotide which binds to various target molecules such as proteins, peptides, lipids and small organic molecules with high affinity and specificity. DNA aptamers specific for the $17{\beta}-estradiol$ were selected by SELEX (Systematic Evolution of Ligands by EXponential enrichment) process from a random DNA library. These DNA aptamers have a high affinity to $17{\beta}-estradiol$ as an endocrine disrupting chemical. Nanowell and $200{\mu}m$ gold electrode were used as substrate for DNA aptamer immobilization and electrochemical analysis. Especially, nanowell gold electrode was fabricated by e-beam lithography. The size of single nanowell is 130nm and 40,000 nanowells were deposited on one gold electrode. The immobilization method was based on the interaction between the biotinylated aptamer and streptavidin deposited on gold electrode previously. Immobilization procedure was optimized by surface plasma resonance (SPR) and electrochemical analysis. After the immobilization of DNA aptamer on streptavidin modified gold electrode, $17{\beta}-estradiol$ solution was treated on aptamer immobilized gold electrode. The current of gold electrode was decreased by the binding of $17{\beta}-estradiol$ to DNA aptamer immobilized on gold electrode. However, in negative control experiments of 1-aminoanthraquinone and 2-methoxynaphthalene, the current was rarely decreased. And more sensitive data was obtained from nanowell gold electrode comparing with $200{\mu}m$ gold electrode.

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Expression Profile of Inflammatory Genes in Human Airway Epithelial A549 Cells

  • Sohn, Sung-Hwa;Ko, Eun-Jung;Kim, Sung-Hoon;Kim, Yang-Seok;Shin, Min-Kyu;Hong, Moo-Chang;Bae, Hyun-Su
    • Molecular & Cellular Toxicology
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    • 제5권1호
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    • pp.44-50
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    • 2009
  • This study was conducted to evaluate the inflammation mechanisms of tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-4 (IL-4), and IL-$1{\beta}$-induced stimulation of A549 human epithelial cells. In the present study, A549 cells were stimulated with TNF-$\alpha$, IL-4 and IL-$1{\beta}$ to induce expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. The effects of TNF-$\alpha$, IL-4 and IL-$1{\beta}$ on gene expression profiles in A549 cells were evaluated by oligonucleotide microarray and Real time RT-PCR. The gene expression profiles for the A549 cells varied depending on the cytokines. Also, the results of the microarray and Real time RT-PCR revealed that inflammatory-related genes were up-regulated in cytokine stimulated A549 cells. Cytokines can affect inflammation in A549 cells. A microarray-based genomic survey is a high-throughput approach that enables evaluation of gene expression in cytokine stimulated cell lines.

Proper Activity of Histone H3 Lysine 4 (H3K4) Methyltransferase Is Required for Morphogenesis during Zebrafish Cardiogenesis

  • Kim, Jun-Dae;Kim, Eunmi;Koun, Soonil;Ham, Hyung-Jin;Rhee, Myungchull;Kim, Myoung-Jin;Huh, Tae-Lin
    • Molecules and Cells
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    • 제38권6호
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    • pp.580-586
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    • 2015
  • While increasing evidence indicates the important function of histone methylation during development, how this process influences cardiac development in vertebrates has not been explored. Here, we elucidate the functions of two histone H3 lysine 4 (H3K4) methylation enzymes, SMYD3 and SETD7, during zebrafish heart morphogenesis using gene expression profiling by whole mount in situ hybridization and antisense morpholino oligonucleotide (MO)-based gene knockdown. We find both smyd3 and setd7 are highly expressed within developing zebrafish heart and knock-down of these genes led to severe defects in cardiac morphogenesis without altering the expressions pattern of heart markers, including cmlc2, vmhc, and amhc. Furthermore, double knock-down by coinjection of smyd3 and setd7 MOs caused the synergistic defects in heart development. As similar to knock-down effect, overexpression of these genes also caused the heart morphogenesis defect in zebrafish. These results indicate that histone modifying enzymes, SMYD3 and SETD7, appear to function synergistically during heart development and their proper functioning is essential for normal heart morphogenesis during development.