PLENARY LECTURE Ⅰ Chemical Biology of Nucleic Acids: DNA Origami and Artificial Genetic Switches Prof. Hiroshi Sugiyama
Kyoto University, Japan

The DNA origami method developed for the preparation of fully addressable two-dimensional (2-D) structures has been utilized for the selective positioning of functional molecules and nanoparticles. We designed a DNA frame using the DNA origami method to investigate enzymatic action and DNA structural change.[1] The substrate dsDNAs were incorporated into the cavity of the DNA frame to allow observation of the behaviors and/or reactions of transcription factors,[2] DNA methyltransferase, DNA recombinase, CRISPR-Cas9, MOC1,[3] and DNA repair enzymes. The proteins that bound to the target dsDNA in aqueous solution on a mica surface were visualized using a high-speed atomic force microscope (hs-AFM). We recently developed DNA nanocages using the DNA origami method and investigated the effect of confined space on the properties of G-quadruplex[4] and i-motif,[5] finding that the mechanical and thermodynamic stabilities of the G-quadruplex inside the nanocage were significantly increased. We also developed a strategy for lipid bilayer-assisted self-assembly of various DNA origami tiles into 2-D lattices.[6] Our results clearly demonstrated that the DNA origami method could provide a unique platform for the analysis of biomolecules at the single-molecule level.
  Our group has also undertaken original research on the molecular recognition of DNA by antitumor antibiotics, and analyzed atom-specific chemical reactions on DNA. By integrating this information, we synthesized various functionalized sequence-specific DNA-binding pyrrole–imidazole polyamides (PIPs), which act as artificial genetic switches that can switch gene expression on and off on demand. We recently developed an alkylating PIP that could switch off the cancer-related KRAS gene[7] and RUNX 1–3 regulatory genes.[8,9] To switch on gene expression we needed to consider epigenetic factors. We also developed a SAHA–PIP complex that comprised a sequence-specific PIP and HDAC-inhibiting SAHA. Evaluation of the effect of SAHA–PIPs on genome-wide gene expression in human dermal fibroblasts demonstrated that each SAHA–PIP could differentially activate therapeutically important genes.[10] Conjugation of the DNA-binding domain "I" with HAT-activating CTB markedly activated the same cluster of genes as SAHA–PIP "I," substantiating the role of PIP in sequence-specific gene regulation.[11] Recently we introduced a bromodomain inhibitor to PIP to activate gene expression in a sequence-specific manner.[12] To extend the recognition sequence, we introduced a host–guest system to facilitate cooperative binding to the target sequence.[13] We can also control the forward/reverse orientation preference of PIP using a cyclic PIP with a chiral amino group.[14]
  In this talk, I will discuss recent progress in molecular analysis using the DNA origami method and regulation of gene expression using specifically designed PIPs.

References
[1] Rajendran, A. et al., Chem. Rev. 2014, 114, 1493.
[2] Raghavan, G. et al., Angew. Chem. Int. Ed. 2019, 58, 7626.
[3] Kobayashi, Y. et al., Science 2017, 356, 631.
[4] Shresha, P.; Jonchhe, S.; Emura, T. et al. Nature Nanotech. 2017, 12, 582.
[5] Jonchhe, S et al., Proc. Natl. Acad. Sci. USA 2018, 115, 9539.
[6] Suzuki, Y. et al., Nature Commun., 2015, 6, 8052.
[7] Hiraoka, K. et al., Nature. Commun., 2015, 6, 6706.
[8] Morita, K. et al., J. Clin. Invest. 2017, 127, 2815.
[9] Maeda R. et al., J. Am. Chem. Soc., 2019, 141, 4257.
[10] Pandian, G. N. et al., Sci. Rep., 2014, 4, 3843.
[11] Han, L. et al., Angew. Chem. Int. Ed. 2015, 54, 8700.
[12] Taniguchi, J. et al., J. Am. Chem. Soc., 2018, 140, 7108.
[13] Yu, Z et al. J. Am. Chem. Soc., 2018, 140, 2426.
[14] Hirose, Y. et al. J. Am. Chem. Soc., in press.

Keywords
DNA nanotechnology; DNA origami; hs-AFM; PIP; genetic switch; epigenetic

CEO초청특별강연 Cosmetic R&D case and future prospects with Biotechnology Sun-gyoo Park
LG Household & Health Care Institute of Technology, Seoul, Korea

Since the discovery of the double helix structure of DNA by J. Watson in 1953, biotechnology has been developed at a rapid pace, expanding beyond traditional medicine and food to a variety of fields including agriculture, electronics, the environment and chemistry. The cosmetics industry is also developing synergies with biotechnology, and has promoted the excellence of Korean cosmetics in the world under the name of "K-Beauty".
With the various brand portfolios such as the Royal palace premium cosmetics 'Whoo' which achieved annual sales of 2 trillion KRW for the first time in Korea, the natural fermentation cosmetics 'SU:M 37º' and the skin science cosmetics 'O HUI', LG Household & Health Care (LG H&H) has developed differentiated cosmetic technology based on the biotechnology and is leading K-Beauty as best cosmetic company in Korea since launching the Korea first skin care cosmetics, Lucky Cream (1947)1.
LG H&H is developing various differentiated cosmetic efficacy ingredients, include oriental medicine ingredients based on the systematic skin oriental medicine theory and the standardized oriental processing method, hypoallergenic fermentation ingredients, and bio-functional ingredients in relation to skin science theory. Furthermore LG H&H has presented new cosmetic technologies such as 'epidermal stem cell activation technology2', 'skin permeation activation technology3', and 'skin exfoliation activation technology4', to maximize efficacy based on biotechnology. Variety of products composed of unique efficacy ingredients and excellent technologies have given a real efficacy of sensory and satisfaction to domestic and overseas customers, resulting in 3 times sales and 4.6 times operating profit over the past decade.
LG H&H is leading the way in R&D as quickly recognizing 'Personalization', one of the future global consumption trends.5 Based on the latest biotechnology, genetic analysis technology, LG H&H is continuously strengthening abilities to analyze and comprehend individual genes/skin characteristics and correlations accurately. Utilizing the vast biological information collected, LG H&H is also trying hard to develop customized products with improved accuracy.
In this lecture, the achievements of LG H&H cosmetics R&D that have been developed with biotechnology are shared, and the current status of biotechnology research for the future cosmetic products is introduced.
References 1. History of Industrial Technology in Korea, Chapter4, 408 (2019)
2. Composition for improving skin (KR 10-1661288)
3. Skin Permeating peptide (KR-10-1329411)
4. S.-H. Lee, S.-H. Jun, K.Yeom, S.-G.Park, C.-K.Lee, N.-G.Kang, Optical clearing agent reduces scattering of light by the stratum corneum and modulates the physical properties of coenocytes via hydration(2018), Skin Research and Technology, 24(3), 371-378
5. Euromonitor, 20 most influential megatrends to shape the world by 2030(2017)

Keywords
Biotechnology; Cosmetics; K-Beauty; LG H&H; Skin science; Personalization; Gene

CEO초청특별강연 Stepwise evolution of Medytox from a start-up to global biotech Gi-Hyeok Yang
Medytox CTO

With continual in-house R&D, Medytox is the only company in the world to develop three different types of botulinum toxin products "Meditoxin", "Innotox", "Coretox", each with its own unique strengths. Along with these products, Medytox has introduced a synergistic hyaluronic acid filler "Neuramis" with its exclusive technology, successfully solidifying the new pipeline. Furthermore, we are now ready for a great leap forward, as all the establishment from Medytox Plant I, Plant II, and Plant III to Medytox R&D Center (Gwanggyo), and Medytox Building in Seoul was constructed.

As a young global biopharmaceutical company established in 2000, we set a goal of entering the 'Top 20 list of global biopharmaceutical companies'. Going forward, Medytox will strive to tackle the advanced markets and to directly penetrate and expand into the emerging markets. We will create meaningful performance with new businesses by increasing investment in R&D and pushing continuous commercialization.

We hope our website (www.medytox.com) can provide you with a chance to learn more about Medytox.

1. Our Products
2. Our Challenge in Global
3. Our Vision: Pipeline for Novel Biologics

Keywords
Medytox; Botulinum toxin; Biopharmaceutical Company