Source: Device House Finishing Self-Sequencing China
Due to the continuous trade friction between China and the United States, the uncertainty faced by the future development of middle and downstream enterprises relying on foreign imported instruments and reagent consumables has increased, and once affected by the trade war, the import price fluctuates, which will have a very large impact on the company's revenue and even the future development of the industry.
However, at present, the domestic genetic testing market is basically monopolized by foreign companies.
Global sequencer market pattern in 2020
According to Grand View Research's 2020 market report, the upstream market size of the global sequencing industry in 2020 is about 4.138 billion US dollars, illumina's market share is about 74%, Thermo Fisher's market share is about 10%, BGI 3%, and other companies' combined share is not more than 20%.
Illumina and Thermo Fisher account for more than 84% of the market, and upstream gene sequencing equipment manufacturing has been monopolized by foreign companies.
China's sequencer market pattern in 2020
The domestic market is still dominated by Illumina, accounting for 61%, Thermo Fisher and other companies together account for about 20%, and BGI (MGI) accounts for about 19%.
However, due to national policies, the two companies want to enter the domestic clinical market, and can only cooperate with midstream sequencing service providers to produce sequencers and apply for NMPA certification.
Noting this development opportunity, at the moment when independent research and development is urgent, with the two core sequencing technologies of the internationally pioneered fluorogenic (Fluorogenic) sequencing chemistry and error correction coding (ECC) sequencing strategy, Xena Bio has developed a fully independently developed sequencing platform from reagents to chips.
01
Two core technologies
Fluorogenic sequencing chemistry
One of the key core technologies of Xena Biotech is Fluorogenic sequencing chemistry.
In 2011, Academician Xie Xiaoliang, co-founder of Xena Biotech, first proposed this technology at Nature Methods. This technique combines the advantages of the current major sequencing techniques to release fluorescent molecules equal to the number of extended nucleotides when the DNA complementary strands are synthesized, and this reaction can be used to achieve low error rate sequencing while synthesizing.
The advantage is that the fluorescent modification is located at the end of the phosphate bond, and when the polymerization reaction occurs, the base is always in its natural state, there is no "molecular scarring", and theoretically the synthesis of DNA molecular chains can be extended infinitely to achieve long reading.
Error Correction Coding (ECC) sequencing strategy
In order to improve the accuracy of high-throughput sequencing, Dr. Chen Zitian, CEO of Syna Biologics, and the team jointly optimized the structure of fluorescent marker molecules in the fluorescence sequencing technology from the chemical principle, designed and synthesized a new fluorescent nucleotide sequencing substrate with excellent reaction performance, tested and modeled the physicochemical reaction process involved in polymerases, optimized the sequencing reaction conditions and signal acquisition process, developed information theory encoding and decoding, etc., and developed the error correction coding (ECC) sequencing strategy after countless improvements and repetitions.
The results were published in 2017 in nature Biotechnology, the top international academic journal.
By organically combining the two core technologies of Fluorogenic sequencing chemistry and error correction coding (ECC) sequencing strategy, on the one hand, the complexity of the sequencing process is reduced, it is easier to measure the long reading length, and the sequencing cost is saved; on the other hand, the high-accuracy error correction decoding algorithm can be used to automatically detect trace sequencing errors that occur during the sequencing process and correct them, which effectively improves the sequencing accuracy. The exclusive design of fluorescently labeled molecules has a high technical threshold and also achieves a high cost performance.
Compared with other sequencing methods, Fluorogenic-ECC error correction sequencing technology can efficiently eliminate sequencing errors after sequencing, further reduce sequencing errors by more than two orders of magnitude, significantly improve the accuracy of current high-throughput sequencing, and greatly expand the space for high-throughput sequencing applications.
S100 with fully independent intellectual property rights
Based on the above two core technologies, the Xena Biological Research Team cooperated in 2017 to develop the first principle machine, namely the S100.
The S100 is easy to use, which not only draws on the advantages of Fluorogenic sequencing chemistry, but also combines a more advantageous error correction coding (ECC) sequencing strategy to reduce the complexity of sequencing, improve the length of reading and accuracy, and the underlying chemical technology can greatly reduce the cost of library-building reagents and personnel costs at the application end.
In September 2017, After receiving the support of the Beijing Municipal Science and Technology Commission for the promotion of science and technology SMEs, Xena Bio began the road of real engineering.
It is understood that the development of Xena Bio Alpha, Beta industrial prototypes, small batch chips and reagents has been completed, and field testing is running well. At the same time, the company has a perfect chemical and enzyme raw materials production base, GMP reagent production workshop, is committed to the manufacture of productionable, cost controllable, easy to operate engineering machines.
After 7 years of steady development, S100, as a domestic gene sequencing platform with fully independent intellectual property rights, can provide more accurate, simple and fast upstream solutions for the gene industry.
At present, the S100 has been finalized and can be quantitatively produced.
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Patent coverage in all fields
The research and development of the gene sequencing platform has extremely high requirements for talents, involving complex molecular biology, chemistry, physics, chips, precision machinery, algorithms and other multidisciplinary and multi-field intersections, high technical thresholds, and strict intellectual property barriers.
Only full replication or technological transformation at the minutiae cannot break the monopoly in the true sense, and it is not easy to achieve true autonomy and controllability.
Syna Bio has a multidisciplinary and interdisciplinary high-quality professional team covering biochemistry, microchip, optical machinery, electronic software and production quality registration in many fields, and has invested a lot of energy in the process of sequencing technology research and development and industrialization.
Xena Bio has applied for 97 intellectual property rights and has been authorized 47
Fluorogenic sequencing chemistry and error correction coding (ECC) sequencing strategies are original sequencing technologies native to China. With the continuous improvement of sequencing technology, Xena Bio has now realized patent coverage in all fields (reagents, equipment, algorithms, chips), and built a powerful moat of intellectual property rights.
Since then, China's gene sequencing technology has an independent core technology and intellectual property rights. According to the information on the official website, the current products of Syna Bio include general-purpose test kits for sequencing reactions, library preparation kits and S100 sequencers.
03
Target the clinical market
The application of the clinical end is one of the most promising application directions of gene sequencing platforms, but there are obvious differences in the demand for sequencing platforms in the clinical markets at home and abroad.
Taking the US clinical market as an example, the US medical system is dominated by centralized laboratories, patients receive medical services in centralized laboratories, the test sample volume is huge, and a large sequencing platform with high throughput is required.
China's health insurance system is completely different from that of the United States, and patients are more likely to complete payments and tests at the hospital end. For Chinese hospitals and small and medium-sized research institutes, large-scale high-throughput sequencing platforms have high start-up costs and do not match actual needs.
Conversely, a small, medium- to low-throughput, fast sequencer is a better choice. In addition to addressing the basic needs of clinical hospitals, breakthrough sequencing technology platforms can also explore the unknown in the course of experiments.
Regarding product positioning, Dr. Chen Zitian said: "The sequencing needs of medical technology departments in domestic hospitals are more inclined to the sequencing platform with low throughput, high accuracy and fast speed, as well as higher cost-effective start-up costs, which is the key to clinical applications. ”
Given that Syna Biologics' current market positioning is primarily for clinical testing, the company's first desktop sequencing platform, the S100, is designed to be a small sequencer that can be flexibly deployed and does not require samples, suitable for hospitals and research institutions.
S100, S200 performance parameters
The Syna BioS100 sequencing platform is characterized by high accuracy, speed, flexible deployment, and no need for samples. In addition, the series of instrument interfaces achieve full Chinese, convenient for researchers to operate, combined with Xena Bio's independent research and development of reagents and chips, etc., can also help partners simplify the sequencing process, reduce sequencing costs, improve industry penetration, and promote the healthy development of the gene sequencing business environment.
Xena Bio has cooperated with several hospitals, research institutions and application service companies in the fields of pathogenic microorganisms, NIPT, PGS, oncology, forensics and other fields, which can meet the diversified needs of scientific research and clinical multi-scenarios.
For example, based on the sequencing platform S100, the Xena Bio-Non-Small Cell Lung Cancer Patient Companion Diagnostic Library Kit (FFPE sample) was used to detect and analyze lung cancer tissue in a hospital in Beijing, and the results showed that it could stably detect mutation information of clinical tumor tissue specimens and guide targeted therapy.
At present, the registration declaration and clinical trial of the S100 sequencing platform of Xena Bio are being carried out smoothly, and it is expected to obtain marketing authorization in 2022. A new generation platform, the S200, is under development and is expected to be available in Q1 2022.
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Construct a new chinese-led sequencing ecosystem
The gene industry has been listed by the state as one of the emerging industries. With the continuous increase of independent research and development and independent innovation in the upstream technology and equipment of gene sequencing in China, domestic sequencers have a certain degree of competitiveness.
In 2015, based on the two core sequencing technologies of Fluorogenic sequencing chemistry and error correction coding (ECC) sequencing strategy, which were pioneered internationally, Dr. Chen Zitian, together with Academician Xie Xiaoliang and Professor Huang Yanyi, founded Xena Biologics.
Founding team
Dr. Chen Zitian, CEO of the company, graduated from Peking University. As a core backbone member, Dr. Chen participated in the major project of "New Generation Sequencer" of the National 863 Program. Dr. Chen has published 19 papers in authoritative journals such as Nature Biotechnology, and as an inventor, he has applied for more than 50 invention patents, authorized 13 and 21 utility model patents.
<h1 class="pgc-h-arrow-right" data-track="112" Academician Xie Xiaoliang of the Science and Technology Committee of the > graduated from the School of Chemistry of Peking University in 1984 and went to the United States to study. Academician Xie is the first scholar to be appointed as a tenured professor at Harvard University (1999) among the scholars who went to the United States in the Chinese mainland after the reform and opening up, a foreign academician of the Chinese Academy of Sciences, and an academician of the two academies of the NATIONAL ACADEMY OF ACADEMIES (NATIONAL ACADEMY OF SCIENCES AND THE NATIONAL ACADEMY OF MEDICINE). </h1>
<h1 class="pgc-h-arrow-right" data-track="114" academician > Xie xie is an internationally renowned scientist with important achievements in the fields of genomics, biophysics, microscopic imaging science and physical chemistry. As a pioneer in single-molecule biophysical chemistry, coherent Raman scattering microscopy, next-generation sequencing technology, and single-cell expansion and sequencing technology, he has made breakthrough contributions in related emerging interdisciplinary disciplines. </h1>
Professor Huang Yanyi graduated from Peking University and has engaged in postdoctoral research at the California Institute of Technology and Stanford University, and is currently a professor at the School of Engineering of Peking University, a researcher at the Biodynamic Optical Imaging Center, a researcher at the Beijing Future Genetic Diagnostics Advanced Innovation Center, and a researcher at the Peking University-Tsinghua University Joint Center for Life Sciences.
Professor Huang was the chief expert and the leader of the overall expert group of the national 863 program "New Generation Sequencer and Supporting Reagents".
In the past 7 years, Sena Biotech has been favored by capital and has completed multiple rounds of financing, with a financing amount of more than 400 million yuan.
Adhering to the corporate vision of "expanding the boundaries of knowledge through technology", Xena Bio is committed to continuously expanding and breaking through the boundaries of knowledge through continuous technological iteration and innovation, redefining "Made in China" with first-class technologies and products, breaking the current status quo of the sequencing market monopolized by foreign-funded enterprises, and building a new ecology of Chinese-led sequencing.
In November this year, Xena Bio will hold a new product launch conference, when everyone is welcome to pay attention to it!