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Research paper : Development of novel chemical reagents for reliable genetic analyses (Y. Komatsu et al.)−3−Synthesiology - English edition Vol.4 No.1 (2011) 4.1.3 Research for practical applicationWe planned the product realization of “high-performance DNA chip” with our joint research companies, by selecting the “ssN-linker” that showed the highest performance among the first-generation types as the terminal modification. The basic data concerning ssN-modified DNA was already completed at AIST, but in order to realize actual use by the bioscience users, it was necessary to clear three major issues: 1) synthesis of the linker reagent, 2) synthesis and purification of the amino-modified DNA, 3) fabrication of the DNA chip using amino-modified DNA and its performance evaluation (Fig. 4a). However, the joint research partner engaging in 3) could not conduct business in chemical synthesis of 1) and 2), and we became painfully aware of the difficulty of realizing a chemical reagent product for use in the biosciences field. Therefore, we set out to explain the function and advantage of the new linker to the chemical companies so that they would undertake the synthesis business of this linker. A certain custom chemical company showed interest in the ssN-linker, and we provided both the linker reagent and the DNA synthesis technologies to this company (Fig. 4b, c). While the technology transfer of mass synthesis of the reagent alone (1) was done easily, time was needed for the technology transfer of synthesis and purification of multiple DNA probes (2). This was because our protocol established in the AIST lab level did not directly fit with that used in the company operating synthesis and purification of several hundreds and thousands of DNAs with automatic machines. That is to say, the protocol had to be adjusted for automation. On the other hand, along with the synthesis work (1 and 2), we also worked on the fabrication of the DNA chip in which ssN-modified probes were immobilized onto the slide glass, and evaluated its function (Fig. 4b, c). Although the work of evaluating the functions of the linkers both upstream (1 and 2) and downstream (3) was extremely hard, for the actual use of the linker by the bioscience users, we believed it was necessary to establish the route and to indicate our product’s superiority to the conventional technology. Therefore, we collaborated with the companies for this work. As a result, we demonstrated that our linker showed higher performance than the conventional reagents in all evaluations, and licensed the manufacture and sales of the ssN-linker modified DNAs to the DNA synthesis company, as well as the sales of DNA chip to the bioscience company.4.1.4 Discovery of issues and interruption of product realizationFor the commercialization of chemical reagents, the stability of the reagent itself and the DNA modified with the reagent are important check items. Since such stability test is generally time-consuming, it was started at AIST at nearly the same time as the technological transfer to the private sector. As a result, while the ssN-linker was stable in the form of a reagent, a slight amount of ssN-modified DNAs were decomposed to lack original property under severe heated alkaline conditions[4]. Since it was stable under ordinary conditions, it was not a major issue in practice. However, the usage and storage greatly depend on users, and we could not negate the possibility that this may develop into a critical problem after it was marketed as a product. Therefore, we decided to halt the licensing of the ssN-linker. We explained the situation to the people involved in both projects of DNA chip fabrication and DNA synthesis, and asked them to temporarily interrupt the projects. The instability of the ssN-linker was an unforeseen result. How much AIST should be involved in product realization including stability testing is a difficult issue. However, we must reflect on the point that we might have rushed the application (downstream) research involving the private companies immediately after discovering the new material, the ssN-linker.4.1.5 Development of the second-generation amino linkerThe interruption of the project was a major setback, and we also experienced a sense of defeat. However, we were Fig. 2 Amino-modified DNA and labeling of nucleic acidsAmino-modified DNA is used for immobilization to the solid surface (a) or bonding with chemical substance (b). The sample DNA (RNA) with the complementary sequence is labeled with the labeling reagent (c). Sample sideRecovery, labeling(DNA、RNA)SampleLabelingreagentaGene detection probessolid surfaceFluorescent dyes etc.Amino linker modified DNALinkerSlide glass, beads, etc.Detection side (probe)bc

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