Break the Monopoly of European and American Manufacturers Gene Sequencing and Promote the Development of Precision Medicine through the Fourth-Generation Gene Sequencer

Introduction

Sequencing the human genome was very difficult. In 2003, the world's first sequencing mapping of the human genome was released, thanks to more than a decade of concerted efforts of a multinational scientist team at a cost of about USD 3 billion. Since then, the scientific community has been developing rapider and lower-cost gene sequencing technologies. Till today, as people show more concerns to health, the market of gene sequencing enjoys a bright future. Precision medicine as a part of the big health industry is developing by leaps and bounds, and the extension of gene testing to clinical medicine will not only boost the development of precision medicine, but also bring convenience to patients in treatment. Roche, a global pioneer in pharmaceuticals, predicted that by 2025, the upstream and downstream market size of gene sequencing will exceed USD 600 billion. From the perspective of the overall gene sequencing industrial chain, gene sequencing equipment is not only the starting point, but also a key link, offering basic support for the middle and downstream gene sequencing services. For the moment, the domestic gene sequencer market is monopolized by European and American manufacturers, and the domestic enterprises are making a concentrated effort on developing new-type sequencers as they seek to break the monopoly. Today, we interviewed Su Yunpeng, Founder of Chengdu Geneus Technology Co., Ltd., a gene sequencer developer, to talk about the important application of gene sequencing in precision medicine and the development of gene sequencer.

Expert Introduction

Su Yunpeng, Founder and CEO of Chengdu Geneus Technology Co., Ltd. (hereinafter referred to as "Geneus Technology") and Senior Expert in Materials Science. He graduated from Northwestern Polytechnical University and obtained a doctor's degree in material processing engineering in 2004; worked as associate researcher at the Hong Kong Polytechnic University from 2005 to 2008; assumed the posts of development manager, supply chain manager and operation director in SAPA, PRATT & WHITNEY and other Global Fortune 500 companies from 2008 to 2017. In 2017, he founded Geneus Technology specializing in the development of nanopore gene sequencer products. In September 2017, the company won the first prize of BioTianfu Cup Precision Medicine Innovation and Entrepreneurship Competition by virtue of the unique advantages of the nanopore gene sequencer project; in 2018, the company's "development of the core component of microflow chip of the 4th generation nanopore gene sequencer" project was approved as part of the "Major Science and Technology Projects of Biotechnology and Medicine in Sichuan Province 2018" by Sichuan Province's Science & Technology Department and won RMB 2 million of fund support.

Su Yunpeng, Founder and CEO of Chengdu Geneus Technology Co., Ltd.

Application of Gene Sequencing in Precision Medicine

Gene testing is the most basic and core technology of precision medicine, providing data base, diagnosis and treatment basis and a prognosis monitoring means for precision medicine. As the data base of precision medicine, gene testing can build a big data sample library for many "omics" such as genomics, transcriptomics and proteomics, and establish associations between genotype and phenotype and links between genetic information and clinical examination, iconography and other data through bioinformatics analysis and genetic diagnosis.

As the diagnosis and treatment basis, gene testing can interpret the sequencing results and distinguish different etiologies and genetic backgrounds of patients with the same disease, and can also compare the sequencing results with the known genotypes and the database for associations between genetic backgrounds and diseases. Doctors can use the comparison results to formulate personalized treatment plans for patients so that "the same disease can be treated with different methods" and "different diseases can be treated with the same method", or use them to predict the risk of diseases to "become best doctors that can cure potential diseases".

As a prognosis monitoring means, gene testing can evaluate the risks of recovered patients and formulate treatment strategies with higher matching degree through sequencing the gene of recovered patients. If the risk is low, excessive treatment should be avoided. If the risk is high, it is necessary to actively apply some auxiliary treatment methods.

In 2017, through the comprehensive utilization of the second-generation and third-generation sequencers, Stanford University succeeded to test the rare disease of "Carney syndrome" and identify the genomic structural variation corresponding to "Carney syndrome". It is the first time in human history to identify the relationship between genomic structural variation and disease through full gene sequencing, which is of great significance and has raised the curtain of rapid development for the field.

In Su Yunpeng's view, precise medicine still faces three bottlenecks in gene sequencing. First is about the cost of human whole gene sequencing. The mainstream second-generation sequencing technology costs about USD 1,000, while the third-generation sequencing technology up to USD 20,000, which is unaffordable for common people. Therefore, to make precise medicine available for the general public, the order of magnitude of the gap should be USD 100 or less. Second, the mainstream second-generation sequencing technology needs more people to do the sequencing by batch to reduce the cost. That makes accepting the sequencing on arrival, and obtaining the sequencing results timely impossible, timeliness, however, is right critical for most clinical applications. Third, the data quality of current mainstream second-generation gene sequencing, especially in read length, coverage and GC bias, cannot meet the requirements of most clinical applications. Take read length as an example. At present, the read length of the mainstream second-generation sequencing is 150 basic pairs. Such a short read length leads to the heavy workload of subsequent alignment and splicing, and more importantly, information on structural variations which account for 76% of the total human genome variations cannot be obtained. In order to solve the above problems, Geneus Technology is developing a new generation of sequencer to break the deadlock.

About the Development Prospects of Precision Medicine

Based on the current development of gene sequencing technology, Su Yunpeng believes that the era of precision medicine will soon come. At present, the precision medicine industry is outrunning the traditional medicine industry, and is expected to reach an annual growth rate of more than 15% in the next five years, three or four times higher than that of the traditional medicine industry. Such a development level and speed depend on the following several aspects. First, the state makes improving national health level and medical treatment level an important strategic objective; second, people are becoming more and more health-conscious. Plus constant technological advancements provide the possibility to meet these requirements.

But due to the bottleneck factors such as the price, timeliness and data quality of gene testing, precision medicine has not yet achieved explosive growth so far. With the commercialization of the new generation of gene sequencers, represented by the nanopore gene sequencer which is currently under development by Geneus Technology, precision medicine is bound to be available for common people, becoming a mainstream medical method helpful for the national health improvement.

About the Entrepreneurship Environment of Tianfu Life Science Park

Committed to making gene sequencing available for common people, Su Yunpeng and his classmates who are senior experts in biochemistry, chip, medical device design, materials and other related fields in China and the United States founded Geneus Technology in 2017. In October 2017, Geneus Technology signed the contract to settle down in Tianfu Life Science Park. Through rapid development, Geneus Technology has now made some progress in software and hardware construction and project research and development. So far, a well-functioning laboratory for protein chemistry and molecular biology, organic synthesis, testing and analysis, chip design, etc. has been established; a high-level research and development team comprised of 17 persons including 3 doctors, 9 masters and 5 undergraduates. On the basis, the development of Geneus Technology is gaining momentum.

When asked about why he chose to start up a business in Chengdu Tianfu Life Science Park, Su Yunpeng mentioned the following factors. "When it comes to this problem, love for hometown comes first. Our founders are all Sichuan locals, so we are more willing to realize our dreams in our hometown. At the same time, during our contact with the government departments of Chengdu Hi-tech Zone, we received a lot of support and assistance from them, and they also gave us some useful advice on settling down in Tianfu Life Science Park." He added that the public platform equipment in the Park can help start-ups save a lot of hardware investment costs in the early stage, and the upstream and downstream pharmaceutical research and development enterprises in the Park can help Geneus Technology form a complete industrial chain.

Su Yunpeng said, "Facts have proved that our choice to settle down in Tianfu Life Science Park is right. Since we settled down in the Park, the leaders of Chengdu Hi-tech Zone and the Park often visit us to learn about our development and provide us with assistance in many aspects, which is an important driving force for the rapid implementation of our research and development projects. In addition, the Park has introduced complete supporting measures which have helped us save investment in fixed assets and carry out research and development quickly."

At present, Geneus Technology has found favor with many investors, and obtains sufficient funds to support research and development. "Going forward, we will, on the basis of comprehensively mastering and optimizing the preparation process of microflow chip, obtain chips that meet the approval requirements of the national medical device regulatory authority and can be mass produced, so that our self-developed fourth-generation gene sequencer can apply them to achieve extensive use in clinical testing." Su Yunpeng is full of confidence in the future development of Geneus Technology.

About Geneus Technology's Flagship Products and Future Plan

In 2018, the "development of the core component of microflow chip of the 4th generation nanopore gene sequencer", a project undertaken by Geneus Technology, was approved as part of the "Major Science and Technology Projects of Biotechnology and Medicine in Sichuan Province 2018" by Sichuan Province's Science & Technology Department and won RMB 2 million of fund support. Only three projects of medical apparatus and instruments in Sichuan Province received the special subsidy. Su Yunpeng said that the special fund will mainly be used in chip biomaterials development and chip tapeout and testing. Within three years, the company will invest over RMB 7 million to realize the overall goals of developing high-performance chips for the fourth-generation nanopore gene sequencer, as it seeks to not only fully master, but innovate and improve the core chip preparation technology.

This fingernail-sized chip can unravel "secret" of gene.

According to Su Yunpeng, Geneus Technology's flagship product, the fourth-generation nanopore gene sequencer, is about the size of an integrated printer, and its core component is a microflow chip used to generate sequencing signals. As a typical, complex systematic project, the R&D of the chip involves protein chemistry, biological material, electronic material, micro electro mechanical system (MEMS), and other fields. The R&D of this type of chip has not yet matured even worldwide, and much remains to be done to improve accuracy, stability, life span, and other dimensions to meet market demand.

Geneus Technology plans to roll out sequencing prototype with 8-16 channels by late 2018, industrial prototype with major functions meeting design needs in 2020, and products for market test in 2021. After the launch of commercial sequencer, the company will gather information of the demands of targeted clients, upgrade products based on clients' demands, optimize properties and functions of equipment, and roll out commercial products in 2022. It is estimated that after three years of the launch of commercial products, annual sales revenue can record RMB 1 billion, and the company is well-poised to break monopoly of European and American manufacturers in gene sequencing in domestic market.