动物实验 z-bo 2020-09-28 428

　　As many marine compounds with significant activity cannot be obtained in large quantities due to limited natural resources, the difficulty in collecting drug sources has become a major obstacle restricting the development of the marine biomedical industry. The application of modern biotechnology such as genomics and synthetic biology is expected to solve the above-mentioned problems.

　　Although the ocean is a “rich mine” for finding medicine, resource development is as difficult as finding a needle in a haystack. According to statistics, marine biomass accounts for 87% of the earth’s total biomass, and there are more than 200,000 species of organisms. However, among the marine natural products that have been isolated and identified, only about 1 have been developed into medicines or entered clinical research. %.

　　As many marine compounds with significant activity cannot be obtained in large quantities due to limited natural resources, the difficulty in collecting drug sources has become a major obstacle restricting the development of the marine biomedical industry. In an interview with a reporter from China Science Daily, many experts believed that the application of modern biotechnology such as genomics and synthetic biology could solve the above-mentioned problems.

　　Medicine source collection encounters obstacles

　　The extracts from the liver of puffer fish can be used as anti-cancer drugs; deoxynucleotides are extracted from the testes of Pacific herrings, which have a significant effect on the proliferation of white blood cells; guanine extracted from the scales of fishes can be used as raw materials for new drugs for the treatment of leukemia... With the declining source of terrestrial medicines, "seeking medicine from the ocean" has become an important direction for innovative drug research and development.

　　The ocean has a unique ecological environment that is different from land, such as high salt, high pressure, hypoxia, and low temperature. This also makes many marine organisms form different metabolic pathways from terrestrial organisms, and produce active ingredients with unique structures but significant pharmacological and toxicological effects. , And most of the ingredients are unprecedented.

　　So far, researchers from various countries have discovered nearly 20,000 natural products from marine animals, plants, and microorganisms. They have shown good development prospects in the fields of anti-tumor, anti-virus, and anti-inflammatory.

　　"Theoretically, there are both terrestrial resources and marine resources. What terrestrial resources do not have, there are marine resources. Moreover, abundant marine resources are not easily exhausted locally like terrestrial resources." Researcher, Dalian Institute of Chemical Physics, Chinese Academy of Sciences Ma Xiaojun said that marine resources are currently rarely exploited, so there is great potential for exploitation.

　　However, compared with developed countries such as the United States, Japan, and the United Kingdom, although my country has a longer coastline and a large area of territorial waters, it has always been in a backward position in the development of marine drugs, and the development of marine drugs is obviously lagging behind terrestrial natural products.

　　"The first thing to bear is the problem of drug source collection." Chen Jisheng, an academician of the Chinese Academy of Engineering, pointed out to reporters that some marine organisms with highly active compounds often have very scarce resources. Due to the particularity of the marine ecological environment, artificial breeding is not feasible. In addition, because the structure of the highly active components of marine organisms is very complex, the cultivation conditions are also very harsh, and the source of medicine is difficult to obtain on a large scale.

　　Zhang Changsheng, a researcher at the South China Sea Institute of Oceanology, Chinese Academy of Sciences, also said that the difficulty of collecting marine medicinal resources is much higher than that of terrestrial resources, and the preservation, preservation, and transportation after sampling need to be considered as a whole. "For the sake of ecological and environmental protection, the amount of samples collected should not be too large to disrupt the ecological balance of the sampling sites." Zhang Changsheng said.

　　Not only that, because my country lacks a systematic assessment of marine medicinal biological resources, the types of resources currently available are very limited, and extreme marine biological resources are hardly utilized. Overfishing has also destroyed the biological chain in the coastal waters, causing many important marine medicinal biological resources to be on the verge of exhaustion.

　　“For this reason, the collection of marine medicine sources is forced to explore the deep sea, and the difficulty of collection has also increased.” Chen Jisheng said. Ma Xiaojun also said that due to my country's short R&D history in the development of marine medicinal resources, few personnel, low investment, and weak integration of disciplines and technologies, it is difficult to utilize marine medicinal resources.

　　Biotechnology solves the problem

　　For a long time, drug research and development in my country have focused on tracking and imitation, and marine drugs are no exception. How to find high-efficiency and low-toxic active natural products from marine organisms and use them through engineering has become a key link in the development of my country's drug development from imitation to innovation.

　　According to reports, most of the existing marine medicines in my country belong to the category of natural medicines, that is, the active ingredients directly extracted from marine organisms. For example, polysaccharides are directly obtained from fish, shrimps and shellfish. The effects of these medicines are often broad. However, some highly active drugs with special curative effects need to be obtained by chemical or biological transformation of the active ingredients of marine organisms.

　　Today, the advancement of synthetic biology technology makes Chen Jisheng full of confidence in the future of marine drug research and development. In his view, synthetic biology will be the way out for marine drug development. "The biosynthetic pathway can be used to engineer the extraction of marine active substances. Of course, the research of this method requires a period of time, not too fast, but it is very promising."

　　Zhang Changsheng also said that with the development of DNA sequencing technology, genome mining, synthetic biology and other related technologies, it will promote the discovery of new medicinal materials and the transformation of existing lead compounds.

　　In his view, synthetic biology technology has high potential in the research and development of marine microbial drugs. "Marine microorganisms have unique advantages as a medicine source. For example, they require a small amount of samples and are environmentally friendly collection; marine microorganisms can be fermented and cultivated in a large amount in laboratories, which are renewable resources, and are easy to transform into synthetic biology technologies to make them oriented. Produce the required products." Zhang Changsheng said.

　　Deng Zixin, an academician of the Chinese Academy of Sciences and a professor at Shanghai Jiaotong University, believes that since most marine microorganisms have the characteristics of short growth cycle, easy regulation of metabolism, and easier breeding of bacteria, large-scale fermentation can be used to achieve mass production of active substances. Solve the problem of drug sources.

　　At the same time, a large number of studies have also proved that the production and accumulation of marine natural active ingredients are not isolated events, they are largely affected by environmental factors. For this reason, Wu Wutong, a professor at the School of Life Sciences and Technology of China Pharmaceutical University, suggested that in order to improve the efficiency of drug discovery and development, it is necessary to integrate the relevant research data of marine organisms’ genes, proteins, metabolites and environmental factors in order to discover new compounds. And provide theoretical guidance for studying new activities of compounds.

　　Many experts also said that they will carry out functional genomics research on marine microbial drug-producing bacteria, find and break through the determining genes and mechanisms related to their marine specific growth, and "domesticate" them into a microbial drug industry that is easy to genetically manipulate and has good fermentation performance. Producing bacteria will also be the focus of marine drug research in the future.

　　Need to increase R&D investment

　　Although the collection of marine medicine sources frequently encounters obstacles, after years of exploration, my country's marine biomedicine research and development has still achieved fruitful results.

　　The "Marine Industry Cultivation and Development Research Report" issued by the Chinese Academy of Engineering shows that currently my country’s self-developed marine drugs include sodium alginate diester, glycerol esters, doenikang, mannitol nicotinate, etc., as well as tetrodotoxin and kidney A variety of marine drugs such as Kang have entered the preclinical or clinical stage, and there are more than 30 generic or secondary derived marine drugs. The marine drugs being developed and the active substances discovered have shown great potential in the treatment of cancer and cardiovascular and cerebrovascular diseases.

　　It can be predicted that with the advancement of marine biomedicine technology, the marine bio-industry will usher in a "golden age" of rapid development in the next 10 to 20 years.

　　However, the development of marine biological resources in my country still lacks top-level design. Jiao Binghua, director of the Department of Biochemistry and Molecular Biology of the Second Military Medical University, expressed concern in an interview with the media: “At the institutional level, the state funding is small and the participation of enterprises is low.”

　　It is understood that from the "Ninth Five-Year Plan" to the "Twelfth Five-Year Plan" period, the state invested less than 1 billion yuan in the development and utilization of marine biological resources; and in the United States alone, more than 50 million yuan was spent on marine drug development and research each year. US dollars; in recent years, the marine drug research funding of the National Institutes of Health has increased to more than 11% of all research funding, basically the same as synthetic drugs and botanicals.

　　In this regard, Ma Xiaojun suggested that the state should increase its investment in research and development of marine drugs, and the internationally accepted enterprise-funded R&D tax credit policy should also be piloted by domestic related marine enterprises. By strengthening the integration of disciplines and technologies, we will promote the development of innovative marine drugs in my country.