The past, present and future of molecular diagnosis

Development of molecular diagnostics

With the DNA double-helical structure model as a symbol, molecular biology has shown its glory and splendor in the development process of more than half a century!

Molecular biology has not only attracted a large number of scientists and clinicians in the world who are interested in understanding the nature of life, but also used life and wisdom to create a waterfall-like academic achievement in the history of medical development, completely changing the traditional concept of diagnosis and treatment. More and more inventions and achievements in the field of biology are being applied in the diagnosis and treatment of various clinical diseases and have greatly promoted the research and development of clinical medicine.

At the same time, molecular diagnostics and treatment have also made considerable progress as a specialized field in the research and application of laboratory medicine and clinical medicine. Molecular diagnosis and molecular therapy have officially entered the historical stage of medical science as an independent discipline.

What is molecular diagnosis?

Molecular diagnosis narrowly refers to a nucleic acid-based diagnosis, that is, the detection of pathogenic mutations in various DNA and/or RNA samples in order to achieve the detection and diagnosis of diseases.

With the publication of the first human genome sequencing map and subsequent publication of other biogenomic sequencing maps, molecular diagnostics has entered a new era with unprecedented opportunities and challenges.

In the post-genome era, with the implementation of proteomics research, the mysteries of the link between functional genomes and their associated expression products and diseases have been solved, and molecular diagnostics has given new extensions: molecular diagnostics include genes and their related Expression products: biological macromolecules.

In a broad sense, gene therapy and biotherapy as well as molecularly targeted therapy for certain signal transduction molecules are included. Over the past few decades, it has shown unique effects in the treatment of certain genetic immunodeficiency, especially neoplastic diseases.

The development of proteomics has become an essential tool for molecular diagnosis. For example, DNA, RNA, protein, chromosome, and cell change spectrum associated with canceration will gradually be recognized by people, and gene mutation spectrum, gene methylation spectrum, gene polypeptide spectrum, and tumor genesis and development will appear. Gene expression profiles, body fluid proteins (or other chemical composition profiles), chromosome profiles, and molecular imaging spectra of cells and tissues and organs. These spectrums of changes will become a spectrum of tumor markers and are more accurately used to guide the prevention, diagnosis, and treatment of tumors.

Molecular diagnosis is a current clinical practice

From Kan and his colleagues first applied DNA hybridization to achieve prenatal diagnosis of α-thalassemia, to Saiki's invention of PCR technology, especially real-time fluorescence quantitative PCR, to high-throughput automated biochip technology and denaturing high-performance liquid chromatography , SNP analysis and other technology applications;

From the use of molecular hybridization, PCR and other single techniques and qualitative diagnostics to the development of multiple techniques for the combined application and semi-quantitative, quantitative and multi-gene disease molecular diagnosis, and then to the diagnosis of biomacromolecules of gene expression products;

From therapeutic diagnosis, to the screening and prophylactic analysis of disease genes or disease-related genes for high-risk populations.

Molecular diagnosis is in the golden age of academic development

With the continuing development of molecular biology theory and technology, molecular diagnostics will be even more brilliant tomorrow.

At the same time, the development of molecular therapies has benefited from the in vitro recombinant DNA technology and lymphoma hybridoma. As a brand-new disease treatment method, gene therapy has developed rapidly in the past 20 years. The implementation of the human genome project and the deciphering of all human chromosomes have not only made humans more aware of themselves, but also laid the foundation for genetic diagnosis and gene therapy research. . Gene technology, gene modification technology, gene cloning technology, gene chip technology, gene therapy technology, and the emergence of new technology and new methods of expression vectors have promoted the development of molecular therapy.

With the in-depth study of the molecular mechanism of tumorigenesis and development, biological therapy including gene therapy has become the fourth model in comprehensive tumor treatment. Biotherapy is based on cutting-edge science such as modern molecular biology, cell biology, and molecular immunology. It emphasizes the molecular basis of tumor development and progression, and the targeted, specific (targeting), and effectiveness of treatment. Targets such as CD molecules, membrane receptor signaling, gene transduction, and angiogenesis, design corresponding drugs (monoclonal or small molecules, etc.), viruses, or cells for the prevention and treatment of tumors. Targeting targets such as CD molecules, membrane receptor signaling, gene transduction, and angiogenesis are currently widely used in cytokine therapy, molecular targeted therapy of tyrosine kinase receptors, and monoclonal antibody labeled radionuclide therapy. .

Biochemotherapy is a new comprehensive treatment mode for the combination of biological therapy and chemotherapy in the treatment of cancer. It is based on the pathological type, clinical stage, site, and development trend of the tumor, combined with the patient's general conditions and molecular biological behavior. A combination of chemotherapeutic drugs and biological agents is planned for treatment.

Gene therapy has broad prospects in the treatment of cancer. Exogenous genes of interest are introduced into human target cells or tissues to replace defective genes through their normal expression to achieve the purpose of preventing and treating tumors. The basic strategies for cancer gene therapy include the following methods: gene replacement, gene modification, gene addition, gene supplementation, and gene cloning. Divided into in vivo gene therapy and in vitro gene therapy according to different ways of functional gene introduction. Commonly used viruses as carriers for gene delivery, there are currently gene-transducing P53 (such as AV-P53), gene-transduced DC (such as AAV-BA46-DC), gene-transduced TIL (IL-2, TNF-α) And so on for each phase of clinical research.

RNA interference technology is also a major breakthrough in gene therapy. By injecting microRNA fragments into the body, it interferes with the organism's own RNA "messenger" function, resulting in the inability of the corresponding protein to synthesize, thereby "turning off" specific genes and using RNA interference techniques to "silence" pathogenic genes directly from the source. Can treat some diseases more effectively.

It is the success of a series of contemporary science and technology that has made the subject of molecular diagnosis and molecular therapy continue to evolve and progress, and molecular diagnosis and molecular therapy are inevitable for the development of contemporary medicine.

China's molecular diagnostics market has broad prospects and its growth rate is double that of the world

The molecular diagnostic market is a hot spot in the clinical diagnosis field in recent years. The global molecular diagnosis market has reached a speed of over 10%, and the Chinese molecular diagnostics market has grown at a rate of more than 20% annually, twice as much as the world, and brings about technological innovation and application. Many development opportunities.

At present, the application of molecular diagnostic products in clinical subjects such as cancer, infection, genetics, etc. accounted for more than 70%, followed by physical examination centers, technical service centers, third-party testing agencies and microbiological rapid detection market.

According to Professor Zhan Qimin, an academician of the Chinese Academy of Engineering and a deputy head of the Chinese Academy of Medical Sciences, “In the field of medical management from the government level to the area of ​​scientific and technological innovation, the application and popularization of molecular diagnostic technology are all attached great importance.” The development of traditional medicine includes diagnosis and treatment methods and improvement of effectiveness. Diagnostic rates, effective prevention, disease early warning, and reduction in morbidity have all encountered bottlenecks that need to be broken.

"To do a good job in transforming medicine and do individualized treatment, we must focus on prevention and prediction, and don't wait until the disease develops until the middle and late stage. This is to guide the disease treatment and move forward. At the same time, we must also focus on moving down. The focus of work is on rural areas and communities, and these areas of work need to be supported by good means and technology platforms. Molecular diagnostics plays a very important role in these links,” Academician Zhan Qimin emphasized.

Looking at the national strategic level, the State Council has listed seven new strategic industries, including biomedicine, in which molecular diagnostics is a very important part.

According to reports, starting from the “Eleventh Five-Year Plan”, the National Natural Science Foundation has searched for some molecular targets in the process of disease development. In the national 973 major projects, combined with clinical research on high-risk diseases, it has provided innovative molecular diagnostics. Achievements. The 863 Program focuses on the application of molecular diagnostics to clinical techniques. It is important to develop molecular diagnosis combined with disease prevention and personalized treatment. In addition, there are application and promotion plans such as industry funds and national major special projects of the National Health and Family Planning Commission, and many of them are related to technological innovation of molecular diagnostics.

Academician Zhan Qimin believes that Holocaust is an international leading molecular diagnostic technology platform R&D and production enterprise, while Suzhou Kebei Bio focuses on the establishment of a molecular diagnostics technology platform and undertakes a number of national-level scientific research projects, such as the national 863 project. Intellectual property. The cooperation between the two sides can not only introduce the most advanced molecular diagnostic technology in the world, but also will be more conducive to localization in the promotion and application in the country.

The use of standards will be introduced in the near future

Li Jinming, deputy director of the National Health and Family Planning Commission's Clinical Laboratory Center, told Science Daily that when people visit medical institutions, doctors will conduct a number of tests on patients first to provide important information for clinical evaluation of patients' disease risks and diagnosis. It is also an important part of medical insurance that doctors determine the suitability of a treatment plan or care for a given patient.

In the past, molecular diagnosis was mainly aimed at the detection of infectious diseases. Now, with the development of personalized technologies, the areas of expansion involve the pathology, pharmacy, and related research departments, such as internal medicine, surgery, and obstetrics and gynecology. Li Jinming, deputy director, said that domestic authorities are drafting guidelines and guidelines for the standardization of clinical molecular diagnostics, and hope to promote orderly development of the market with clear management methods and rules. The standards for the use of molecular diagnostic technology platforms will also be introduced in the near future.

Transnational cooperation is optimistic about the application of localization

The strategic cooperation between Haoluojie and Suzhou Kebei Bio is generally optimistic. Academician Zhan Qimin believes that both the competent authorities and experts are happy to see and support this international cooperation. I believe both parties can find better models to produce more positive results. Li Jinming, deputy director of the hope that through the introduction of the international advanced platform to promote the relevant technical standards in the country can be in line with international standards.

Liu Luojun, a vice president of Haoluojie, told a reporter from Science and Technology Daily that Haoluojie, a listed company providing medical instruments and detection systems, has a market value of US$5.7 billion. His molecular diagnostic core technology won the 2004 National Technology Award. The company's product focus is mainly on disease diagnosis, blood screening, and ensuring the compatibility of the transplant to improve early detection and minimally invasive treatment through early screening and screening to achieve the goal of saving lives in time.

If a multinational company wants to better serve the medical market in China, it must be grounded, truly understand the market, understand the policies and regulations, including market operations, and achieve a strong and unified classic model. “We finally decided that we should be cautiously considering merging with Corbett. There are two reasons for this. The first is that Corbett’s national R&D institution backed by Beijing can greatly shorten the cycle from scientific research to commercial application. Shellfish has independent third-party testing qualifications, its business operations are also very complete, and it also has strong resources in hospitals and medical systems,” Liu said. He hopes that Hao Luojie will jointly develop new localization applications with the advanced molecular diagnostics automation platform and Kebei Biosciences, and push China's molecular diagnostics business to a new height.

According to Ji Yun, President of Suzhou Kebei Bio, the project is an attempt to “run parallel” commercial cooperation model. On the one hand, it is possible to conduct research and development with products with independent intellectual property rights, and on the other hand, it is necessary to strengthen international cooperation and accelerate the promotion of mature technology platforms, instruments, and products from abroad.

He said, "Science has no national borders. Our overall level in medicine is currently far from the developed countries in Europe and America. However, China is a country with large clinical needs and is currently moving toward becoming a strong country. Kebei Life is very familiar with domestic hospitals and the public. With regard to the needs of molecular diagnostic technology, the cooperation between the two parties will not only be the development of their respective companies, but will also benefit the general public and the patients from the new medical results. The introduction of more advanced technologies and common development is our responsibility. Long-term development goals."

The cooperation between international giants and leading domestic companies will help the domestic molecular diagnostics industry to gain a foothold in local gas, strengthen localization, and widely popularize and promote this emerging technology.