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2019/08/14

Session2-3 Solution provider for new pharmaceutical modalities

Shin-Il Kim ~aceRNA Technologies~

[Summary]

You have a situation where two cell types are mixed together. If one cell type is unwanted or has a potential risk, how would you eliminate one over the other? The answer is that our technology can achieve it. RNA SwitchTM is designed for two applications. First, specific cell type purification (enrichment and elimination) from small to large scale using an activity of specific microRNA (miRNA) of your cell type. Second, drug discovery for the highly active miRNAs in your cells by using RNA SwitchTM library platform.
How does RNA SwitchTM work? RNA SwitchTM is a synthetic messenger RNA (mRNA). Upon an entry of cell, it doesn't enter the nucleus, so it doesn't harm the integrity of the genome. Therefore, it is generally considered as a safe method. The synthetic mRNA contains the complementary sequence of the target miRNA which is linked to apoptosis inducing or GFP reporters. For example, in the presence of target miRNA, an endogenous miRNA binds to the mRNA and degrades leading to lower GFP expression or lower apoptosis, so cells express less GFP and can stay alive. However, in the absence of target miRNA, you can have a strong GFP expression. By observing a strong fluorescence level, you can screen which miRNAs are highly active in your cell types. In addition to this, in the absence of the target miRNA, it will induce apoptosis. What we have achieved so far in terms of the cell purification, hepatocytes, neurons, cardiomyocytes, and insulin producing cells have been purified among the populations derived from human induced pluripotent stem (iPS) cells based on their cell type specific miRNAs. iPS cells remaining after the iPS differentiation into somatic cells can be dangerous. We have been able to eliminate remaining iPS cells with RNA SwitchTM technology.
Let's switch gears to drug discovery. We have built up 2657 RNA SwitchTM library platform in the form of 96 or 384 well format. When you transfect it into your cell type and if you can observe lower GFP expression, it means that you found specific miRNAs in your target cells. After whole screening, when you assemble all GFP expression data, you can generate diagram/graph showing cell type specific highly active miRNA expression throughout an individual cell type.
Traditional method to find active miRNAs has been using Microarray based on miRNA levels. However, we have observed that not all highly expressed miRNAs respond to our RNA SwitchTM, suggesting that highly expressed miRNA often doesn't have an activity. So, for the future, we will examine highly expressed miRNA which has a high activity or more importantly, you can search for lower expression but highly active miRNAs.
RNA SwitchTM technology was invented by Hirohide Saito, who is a professor and vice director in Center for iPS Cell Research and Application (CiRA), where iPS pioneer Prof. Shinya Yamanaka serves as a director. Dr. Teruho Susumu who is a CEO of our company has much experience in industry, pharmaceutical companies, and venture capital/partnering groups. We have a financial support from the Kyoto University Innovation Capital. As a R&D director, I have developed my research career in Korea, USA, and Japan over long periods. We are a good team and therefore, we believe that we can help you to achieve your goals.
We are looking for alliances and collaborative research partners for regenerative medicine and drug discovery using RNA SwitchTM technology. For example, if you have a contamination with other cell type in your culture, we can eliminate unwanted cells or enrich your target cells. Now, we are working with several companies for the goals, iPS cell elimination and cardiomyocyte purification. Additionally, for the drug discovery, we are looking for collaborators to find highly active miRNAs in your target cells for the next drug discoveries.

[Profile]

kim.JPG I obtained Ph.D in 2008 from University of Wisconsin - Madison. After a postdoc at University of California - SF, I received JSPS Postdoctoral Fellowship to study iPSCs at CiRA, Kyoto University under supervision of Drs. Yamanaka and Woltjen. Currently, I am a director of R&D division at aceRNA Technologies.