Vol.4 No.1 2011

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Research paper : Development of novel chemical reagents for reliable genetic analyses (Y. Komatsu et al.)−8−Synthesiology - English edition Vol.4 No.1 (2011) what has brought you to your “scenario to contribute to the improvement of precision of the overall genetic analysis” and explain why you “selected to fulfill the demand in the niche field” in that process. This will enable the readers to understand the authors’ thinking processes.Answer (Yasuo Komatsu)I rewrote the text to clarify the explanation of the figure and the scenario. Also, I created a simple table that summarizes the advantages and the disadvantages of the amino linkers.2 “3.1.4 Discovery of the problem”Comment (Yoshifumi Jigami)This is an important section that explains the motivation for the development of the second-generation amino linker and I think you should give a more detailed explanation. Particularly, there should be a more elaborate explanation of your decision and the situation why the discovered problem halted the licensing of the ssN-linker and interrupted the project.Also, I think the significance in terms of synthesiology will be clear if you add your thinking and social situation behind “the decision to allow the developed product to be used by Japanese and overseas companies despite the decrease in royalties”.Answer (Yasuo Komatsu)At the same time that ssN-linker showed high reactivity, it was also chemically unstable. The transformation of ssN-linker is confirmed only under limited conditions. However, the situation under which the users store the amino-modified DNA may vary greatly, and we could not eliminate the possibility that the linker may transform during storage and its function may decrease. This means that if such a compound with potential danger is released to the public sector, the company must carry the risk. Therefore, although the project was far in its course, we made a decision to develop a better linker. The background of making such a decision immediately before licensing was mainly from a thought that claims from users could be extremely troublesome to deal with, as well as a vague feeling that there was a possibility of some major problem in the future.We considered licensing not only in Japan but overseas from the beginning of the R&D. We made this decision because having the developed technology used throughout the world will expand the possibility for evolution of this technology. For royalties, rather than AIST profiting, we thought it was more important that businesses would be conducted in the private sector as shown in Fig. 4. 3 “3.2 Labeling reagent”Comment (Yoshifumi Jigami)I think it would be more useful to the readers if you compare the property of the newly developed reagent with that of the conventional reagent and comment on how much and what kind of social impact will arise from future developments based on this new agent.Answer (Yasuo Komatsu)The high reactivity of the developed labeling reagent to the nucleic acid will lead to the reduction in the amount of reagent needed for the detection of minute amount of samples (reduction of background value). The characteristic in the structure of the reagent also provided an important finding in the creation of the nucleic acid recognition molecule other than the labels. I rewrote the text to emphasize these important points.4 “4.1 Development of the research”Comment (Hisao Ichijo, Tsukuba Center, Inc.)I think it will be easier to understand and the readers will be able to see the choice of the research elements conducted in the R&D process, if you explain the process by which you arrived at the new labeling reagent.Answer (Yasuo Komatsu)If there was no development of the second-generation reagent, there would have been no realization, and this was a major point. As you indicated, I added the importance of this development in the discussion section.Comment (Yoshifumi Jigami)You state, “the fact that we selected a ‘non-trendy development’ turned out to be important (Factor 1)”. If that is true, you should explain why this is important. You should also describe a specific situation how “the collaboration inside and outside the institute to conduct wide-ranging research for product realization (Factor 2)” has been carried out.For the Development 3 of Fig. 7, please present a discussion on how the seeds-oriented research is different from the earlier needs-oriented research and what are your assumptions on how the difference of research methods affect the research results and what kind of ripple effect (social impact) there may be in “5 Future issues”. Also, it seems you are returning to a seeds-oriented research from the earlier needs-oriented research, but as a researcher, why do you need such a return? I would like to hear the “thoughts” and “future dreams” of the authors based on this experience.Answer (Yasuo Komatsu)Pursuing a trendy topic means that the research may be an attempt to catch up to someone else, and may end up without ever catching up if we are lacking human resource power. On the other hand, technology that was once thought to be firmly established may develop problems due to new demands arising from changes over time. Therefore, we reviewed the technology that was considered firmly established, dug up its problems, and that led to good results for this particular case. I rewrote the part that explains the other factors that led to the success. I also added some text in Fig. 6.For demand and potential, or “needs and seeds”, we engaged in “needs-oriented” research in the first two R&D. However, as written in the text, if we are caught up by “needs” only, we must compete with (that is, replace) the similar, existing technologies. It may be difficult to replace the already entrenched technology even if the new technology is superior, and this requires time. We wanted to try the route of providing a technology with absolutely no similar product, and then move toward its product realization. Therefore, we began the development of the third reagent. However, such approach may land in a place where the demands are different. Therefore, I don’t know what the best approach is, but both elements are required in practical use, and I personally think that a balance has to be struck and modifications made in the process of the research.

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