• Title/Summary/Keyword: Genome Editing

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Identification of neoantigens derived from alternative splicing and RNA modification

  • Park, Jiyeon;Chung, Yeun-Jun
    • Genomics & Informatics
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    • v.17 no.3
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    • pp.23.1-23.6
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    • 2019
  • The acquisition of somatic mutations is the most common event in cancer. Neoantigens expressed from genes with mutations acquired during carcinogenesis can be tumor-specific. Since the immune system recognizes tumor-specific peptides, they are potential targets for personalized neoantigen-based immunotherapy. However, the discovery of druggable neoantigens remains challenging, suggesting that a deeper understanding of the mechanism of neoantigen generation and better strategies to identify them will be required to realize the promise of neoantigen-based immunotherapy. Alternative splicing and RNA editing events are emerging mechanisms leading to neoantigen production. In this review, we outline recent work involving the large-scale screening of neoantigens produced by alternative splicing and RNA editing. We also describe strategies to predict and validate neoantigens from RNA sequencing data.

Recent advances in developing molecular tools for targeted genome engineering of mammalian cells

  • Lim, Kwang-Il
    • BMB Reports
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    • v.48 no.1
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    • pp.6-12
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    • 2015
  • Various biological molecules naturally existing in diversified species including fungi, bacteria, and bacteriophage have functionalities for DNA binding and processing. The biological molecules have been recently actively engineered for use in customized genome editing of mammalian cells as the molecule-encoding DNA sequence information and the underlying mechanisms how the molecules work are unveiled. Excitingly, multiple novel methods based on the newly constructed artificial molecular tools have enabled modifications of specific endogenous genetic elements in the genome context at efficiencies that are much higher than that of the conventional homologous recombination based methods. This minireview introduces the most recently spotlighted molecular genome engineering tools with their key features and ongoing modifications for better performance. Such ongoing efforts have mainly focused on the removal of the inherent DNA sequence recognition rigidity from the original molecular platforms, the addition of newly tailored targeting functions into the engineered molecules, and the enhancement of their targeting specificity. Effective targeted genome engineering of mammalian cells will enable not only sophisticated genetic studies in the context of the genome, but also widely-applicable universal therapeutics based on the pinpointing and correction of the disease-causing genetic elements within the genome in the near future.

Current Strategies of Genomic Modification in Livestock and Applications in Poultry

  • Park, Tae Sub
    • Journal of Animal Reproduction and Biotechnology
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    • v.34 no.2
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    • pp.65-69
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    • 2019
  • Since the development of the first genetically-modified mouse, transgenic animals have been utilized for a wide range of industrial applications as well as basic research. To date, these transgenic animals have been used in functional genomics studies, disease models, and therapeutic protein production. Recent advances in genome modification techniques such zinc finger nuclease (ZFN), transcription activator-like effector nucleases (TALEN), and clustered regularly interspaced short palindromic repeats (CRIPSR)-Cas9, have led to rapid advancement in the generation of genome-tailored livestock, as well as experimental animals; however, the development of genome-edited poultry has shown considerably slower progress compared to that seen in mammals. Here, we will focus primarily on the technical strategies for production of transgenic and gene-edited chickens, and their potential for future applications.

A Simple Java Sequence Alignment Editing Tool for Resolving Complex Repeat Regions

  • Ham, Seong-Il;Lee, Kyung-Eun;Park, Hyun-Seok
    • Genomics & Informatics
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    • v.7 no.1
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    • pp.46-48
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    • 2009
  • Finishing is the most time-consuming step in sequencing, and many genome projects are left unfinished due to complex repeat regions. Here, we have developed BACContigEditor, a prototype shotgun sequence finishing tool. It is essentially an editor that visualizes assemblies of shotgun sequence fragment reads as gapped multiple alignments. The program offers some flexibility that is needed to rapidly resolve complex regions within a working session. The sole purpose of the release is to promote collaborative creation of extensible software for fragment assembly editors, foster collaborative development, and reduce barriers to initial tool development effort. We describe our software architecture and identify current challenges. The program is available under an Open Source license.

DNA Barcoding of Isaacsicalanus paucisetus (Copepoda: Calanoida: Spinocalanidae) from the Hydrothermal Vent in the North Fiji Basin, Southwestern Pacific Ocean

  • Park, Chailinn;Lee, Won-Kyung;Kim, Se-Joo;Ju, Se-Jong
    • Animal Systematics, Evolution and Diversity
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    • v.36 no.2
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    • pp.182-184
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    • 2020
  • Isaacsicalanus paucisetus Fleminger, 1983, a monotypic species of the family Spinocalanidae Vervoort, 1951, was first reported from a hydrothermal vent field in the East Pacific Rise off the mouth of the Gulf of California. The mitochondrial cytochrome oxidase I(mtCOI) DNA barcodes are considered a useful tool to assist traditional taxonomy and species discrimination in calanoid copepods. However, the mtCOI DNA barcodes of I. paucisetus have not been reported due to the species rarity and the difficulty of sampling. In this study, we firstly determined the mtCOI DNA barcodes of the I. paucisetus newly collected from a hydrothermal vent in the North Fiji Basin of the southwestern Pacific. All mtCOI DNA barcodes of I. paucisetus were identical and intraspecies variations of spinocalanid species were 0.0-3.0%. Interspecies and intergeneric variations were 13.4-25.2% and 16.7-24.1%, respectively. The DNA barcodes of I. paucisetus obtained in the present study would be helpful for understanding taxonomic relationships of widespread spinocalanid species.

An NMR study on the intrinsically disordered core transactivation domain of human glucocorticoid receptor

  • Kim, Do-Hyoung;Wright, Anthony;Han, Kyou-Hoon
    • BMB Reports
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    • v.50 no.10
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    • pp.522-527
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    • 2017
  • A large number of transcriptional activation domains (TADs) are intrinsically unstructured, meaning they are devoid of a three-dimensional structure. The fact that these TADs are transcriptionally active without forming a 3-D structure raises the question of what features in these domains enable them to function. One of two TADs in human glucocorticoid receptor (hGR) is located at its N-terminus and is responsible for ~70% of the transcriptional activity of hGR. This 58-residue intrinsically-disordered TAD, named tau1c in an earlier study, was shown to form three helices under trifluoroethanol, which might be important for its activity. We carried out heteronuclear multi-dimensional NMR experiments on hGR tau1c in a more physiological aqueous buffer solution and found that it forms three helices that are ~30% pre-populated. Since pre-populated helices in several TADs were shown to be key elements for transcriptional activity, the three pre-formed helices in hGR tau1c delineated in this study should be critical determinants of the transcriptional activity of hGR. The presence of pre-structured helices in hGR tau1c strongly suggests that the existence of pre-structured motifs in target-unbound TADs is a very broad phenomenon.