Domestic instruments bright sword gene sequencing market

Despite the increasing interest in gene sequencing in recent years, China, as the most populous country in the world, has also shown great market potential in this area. The market for prenatal diagnosis in this application area has been estimated. About 15 billion yuan. However, in the face of such a big cake, according to incomplete statistics, China now has hundreds of companies providing gene sequencing services, but the main suppliers of gene sequencing equipment are only Illumina and Life Technologies (now acquired by Thermo Fisher). Family. Moreover, these two suppliers not only monopolize the Chinese market, but also share nearly 90% of the global gene sequencing instrument market.

In the face of such a strong competitor, there are still several domestic units that have been devoting themselves to the development of gene sequencing devices for many years. In April this year, a prototype of a new generation of gene sequencer jointly developed by the Beijing Institute of Genomics, Chinese Academy of Sciences and Jilin Zhongxin Zixin Technology Co., Ltd. was officially unveiled.

Localization is a long way

Due to its monopoly status, the price of foreign gene sequencing instruments and reagents in China is often higher than that of the country. The cost of performing the entire sequencing in foreign countries may only be enough to buy reagents in China. As the world's largest supplier of genetic sequencing instrument reagents, Illumina's reagent prices are priced globally at 4% annually. Huada Gene purchased 128 Illumina's HiSeq 2000 sequencers in 2010, but due to the price of the reagents, the cooperation with Illumina gradually alienated. After that, BGI acquired the American Complete Genomics (CG) company and started cooperation with Life Technologies.

Dr. Lu Feng, researcher of the DNA sequencing technology research and development center of the Beijing Institute of Genomic Sciences, Chinese Academy of Sciences, said: “For us, it is very important to change the market pattern that is controlled by people, and provide cost-effective products for domestic users. ."

Ren Lufeng and the prototype of a new generation gene sequencing machine made in China

Speaking of the cooperation between the Beijing Genomics Institute and Zixin Pharmaceutical, they signed the "Sequencer Project Investment Intent for Industry Conversion" at the opening ceremony of the International Genomics Congress on October 29, 2013 to jointly develop a gene sequencing device. However, both parties actually started cooperation in the Chinese Ginseng Genome Project since 2010. Perhaps because of the trust built up by the previous cooperation and the optimistic view on the market prospects of gene sequencing, Zixin Pharmaceutical dared to invest a great deal of money to promote the localization of gene sequencing devices. According to reports, in this project, Zhongke Zixin plans to invest 100 million yuan and invest 20 million in the initial stage. It plans to build a 500-1000 gene sequencing machine production line in Jilin this year.

The road to product development combined with users

The new generation of gene sequencer uses pyrophosphate emission sequencing technology, which uses a similar gene sequencing technology with Roche454. The sequencing read length can now exceed 750bp, after further optimization, it can reach 1000bp, and the maximum throughput for single sequencing is 400M. Up to 400,000 reads. Ren Lufeng said: "In 2011, we used the prototype of the product to conduct bacterial sequencing and published an article. No unit in the country has "showed" its own equipment like us."

It is understood that the chip of the gene sequencer, as well as data analysis software, etc. will be domestically produced, the cost of which is lower than 1/3 of the imported equipment, and the application cost is less than 1/5 of the imported equipment. The instrument has now obtained 8 granted patents, mainly focused on the principle of technology, and plans to file 100 patent applications this year.

Ren Lufeng introduced: “After the successful development of this instrument prototype, we first worked with a pharmaceutical company to analyze the sequence information of certain engineering bacteria. In the second half of this year, we plan to complete the research and development of the pilot process and introduce 20 trial machines. , 20 test units including medical treatment, inspection and quarantine, disease prevention and control, universities, research institutes, etc. are used for free testing.The test work mainly includes the optimization and improvement of the system performance, and the application of the product according to the different applications. Joint development, that is, a series of special reagent products derived from the platform of the basic reagent product, and the development of corresponding data analysis algorithms and databases to achieve a comprehensive solution for the practical application of sequencing technology.”

Let 20 units try out, in addition to the needs of product development, Ren Lufeng said: "We hope to let everyone to evaluate this instrument in the end easy to use and not easy to use. Domestic instruments always have a process that is approved by the user, we are the most What needs to be done is to make every effort to improve the stability of the instrument and allow the user to accept it. There are many domestically produced instruments that have been made in the first place and have been rigged, thus directly undermining the confidence of users in domestically produced instruments."

The mainstream second-generation sequencers currently on the market can only perform parallel sequencing of the amplified sequences. Therefore, the third-generation gene sequencer capable of sequencing a single DNA molecule has attracted the attention of many research institutions. In this regard, Ren Lufeng said: “The third-generation gene sequencer has faster data reading speeds. We also thought about developing such instruments, but later we still plan not to do it first because the technology has a serious drawback. The accuracy of sequencing is insufficient, and it is currently only about 85%, so our next plan is still the second-generation sequencing technology, and next year we will develop instruments that use semiconductor technology sequencing, reading length can exceed 2000bp, original accuracy rate If 99.9% is achieved, the cost will be further reduced. If it goes well, it is expected that the prototype will be available by the end of 2016."

Photo of a new generation of gene sequencing team made in China

Market is big and responsibility is bigger

The market for gene sequencing can be said to be infinitely large. While there are potential markets for the main application fields of clinical diagnosis of the gene sequencer, the current situation is not optimistic. At the end of last year, the US FDA suspended the health analysis business of 23andMe, a personal genetic testing service company. The National Health Planning Commission and the Food and Drug Administration also called for the clinical application of the gene sequencer after the Spring Festival this year, announcing that it includes all of the prenatal genetic testing. Medical devices that require the use of testing instruments, diagnostic reagents, and related medical software, such as for disease prevention, diagnosis, monitoring, treatment monitoring, health status assessment, and prediction of genetic diseases, must be approved by the food and drug regulatory authorities for registration. All relevant products are required to apply for strict declarations, and only after they have obtained a registration certificate can they be used clinically.

“The market for clinical diagnosis is very big, but the responsibility is also very large. It can be said that the clinical is no small matter, so I have not been very active in this field of application. At present, there is no standard for clinical diagnosis of gene sequencing devices in China. The technology, methods, equipment, and reagents have not been certified by the CFDA, so the risk is also very high, so it is necessary for the country to stop.” Ren Lufeng said.

In the face of the country's suspension, in order to speed up the approval process, both Illumina and Life Technologies have chosen to cooperate with domestic sequencing service companies for OEM production. For example, Illumina is working with Berry and Kang to produce a new sequencer, and Life Technologies Collaboration with Huada Gene and Daan Gene to develop a new product based on the Ion Proton sequencing platform. Although the products of this model use foreign instruments and technologies, the declaration of CFDA is based on the channels of domestic instruments and equipment. The application and approval are relatively fast. If the progress is smooth, the normal audit time for such equipment in China will be about 1-1.5 years.

Since the gene sequencer is an open platform, it can carry out almost all kinds of clinical sequencing applications. After the procurement in the hospital, it is difficult to be replaced in the short term. When the country called for the clinical application of the gene sequencing device, we also speculated that in addition to the clinical application market for gene sequencing, there may be other implications. When the country calls for gene sequencing, it is precisely in the interest of domestically-related companies to achieve industrialization and make up for their late entry into the market. However, in the face of such "domesticized" offensive tactics for imported instruments, the disadvantages of domestically produced sequencing machines are even more obvious. If they miss the opportunity, they will undoubtedly pay a greater price.

Ren Lufeng said: “We used to always say that the wolf had come. This time, the wolf really came. Everyone has been talking about domestic production. The result is a group of wolves dressed in coats made in domestic instruments. Of course, this also gives us even greater pressure. And power to do our genetic sequencing."