"The 2023 Nobel Prize in Physiology or Medicine will be awarded to the discoverer of nucleoside base modification, which is not 'pie in the sky'." Zhang Lihe, academician of the CAS Member, said at the Xiangshan Science Conference held recently on the theme of "nucleic acid biological structure chemistry and biomedicine and health" that the two winners had done detailed research as early as 2018. They found that when messenger ribonucleic acid (mRNA) contains pseudouracil base modifications, the inflammatory response in the human body is basically eliminated, which makes the development of effective mRNA vaccines a reality. During the COVID-19 epidemic, nucleic acid research attracted much attention; This year it entered the public eye again due to the Nobel Prize. The rise of nucleic acid drugs has opened up a new direction for new drug research and made gene therapy and personalized therapy possible. As the executive chairman of this meeting, Zhang Lihe gave a keynote speech on the development of nucleic acid drugs. Experts attending the meeting believe that nucleic acid research is facing significant development opportunities, and China should accelerate the promotion of multi-scale cross research in the field of nucleic acid, especially in the fields of nucleic acid biological structural chemistry, biomedicine, and health research, to promote basic research in life sciences and the rapid development of the biotechnology industry. Nucleic acid drugs have entered a period of rapid development. "As the most essential objective existence of life phenomena, nucleic acid is the material carrier of genes," said Huang Zhen, executive chairman of the conference and professor at the School of Life Sciences, Sichuan University. Nucleic acid drugs have great potential for development, "Zhang Lihe introduced. Nucleic acid drugs are drugs that regulate, inhibit, or silence gene expression to achieve therapeutic effects. These drugs use oligonucleotides as the basic structure and target mRNA through hydrogen bonding interactions. The targets of traditional chemical small molecule drugs are mostly proteins. But in the human genome, the genes encoding proteins account for less than 1.5%. However, according to drug statistics approved by the US Food and Drug Administration (FDA), as of January 2017, there were a total of 856 protein based targets among all patent drugs, accounting for over 95% of all targets. Therefore, theoretically speaking, there are still a large number of nucleic acid targets that can be explored in the process of drug innovation. Zhang Lihe said that in the past, proteins were used as targets because they came from specific mRNA sources. Therefore, regulating the levels of mRNA or mRNA precursors to treat diseases has become a long-term and sustained pursuit of pharmaceutical chemists. At present, this has become a new field. In the past, the traditional understanding in the field of drug research was that oligonucleotides were difficult to become drugs. So, the task of pharmaceutical chemists is to make it easier to synthesize oligonucleotide drugs, including how to make them more convenient to synthesize, stable in organisms, easy to enter cells, and specifically bind to target nucleic acids. At present, the problems of oligonucleotides' medicinal properties and the delivery of nucleic acid drugs have been basically solved, and the advantages of nucleic acid drugs have become increasingly apparent. "Zhang Lihe introduced that the advantages of nucleic acid drugs mainly include short research and development cycles, fast drug target screening, less susceptibility to drug resistance, wider treatment fields, good safety, long-lasting effects, and higher clinical research and development success rates. Zhang Lihe stated that in the past five years, the investment in small nucleic acid drug research has maintained a good trend of double-digit growth, which has sparked research by domestic and foreign pharmaceutical companies
Edit：Ying Ying Responsible editor：Shen Chen
Source：digitalpaper.stdaily.com
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