Yi Kang Gene CEO Lu Sijia: Single Cell Sequencing Technology Creates a New Chapter of Precision Medicine

BY Dr. Lu Sijia:
Single cell sequencing is the ultimate in life science research

Yi Kang Gene General Manager and Co-Founder
MALBAC® inventor, published a total of dozens of SCI first round papers

Sequencing China talked about Dr. Lu Sijia, general manager and co-founder of Yikang Gene, a well-known enterprise in the field of reproductive health. Dr. Lu Sijia is the inventor of the MALBAC® single-cell whole genome amplification technology. This technology has made significant progress in the fields of assisted reproduction, prenatal diagnosis, prenatal and postnatal care, and tumor screening, and has been successfully applied in clinical applications. In an exclusive interview, Lu Sijia talked about his cross-border research experience, his understanding of life and his pursuit of science.

"I am a typical cross-border scientific researcher"

Dr. Lu Sijia's undergraduate degree at Fudan University specializes in physics and optics, and is engaged in the research of precision systems such as laser systems, ultrafast optics, and microscopes. At that time, the second-generation sequencing technology was just getting started. How to apply the accurate detection of optics to the second-generation sequencing that was just started, became the biggest driving force for Dr. Lu to go to Harvard to study.
After graduating, Dr. Lu came to Harvard University as he wished, and studied under Professor Xie Xiaoliang, an internationally renowned chemist and academician of the American Academy of Sciences. After entering Harvard, the single cell amplification research project led by Xie Academician was launched. Dr. Lu Sijia's research field has gradually shifted from the field of optical physics to the field of genes, and started the second generation sequencing in the long-term career of 5 years. Research.
Dr. Lu responded humorously as a typical cross-border scientific researcher, swimming between physics, chemistry, ultrafast optics, genomics, genetics, embryology and other fields. Genomics and gene sequencing are inherently cross-border and do not belong to any traditional research direction. The identification of chemical reactions, optical visualization, and engineering and algorithmic support throughout the sequencing process are all essential technological factors for gene sequencing.
Dr. Lu Sika also felt very much about his own scientific research experience and the wave of gene sequencing technology in the first two decades of this century. "I think that the future scientific progress, from NGS to genomics, will be a multidisciplinary blend. Based on this, I believe that the domestic education system and industrial system need to be further reformed to adapt to the new environment and new changes. Most foreign laboratories have the characteristics of multidisciplinary integration, such as engineering, physics and chemistry in our group. Computers and other members, but this situation is rare in China. China's sequencing industry can only accelerate to a new level after the reform of the education system, scientific research system and industrial system."
In addition, Dr. Lu particularly emphasized the importance of the “production, study and research” cooperation on the transformation of scientific and technological achievements. He said: "From the perspective of the development of various industries in China, the foundation of 'production, study and research' is not very good. In the United States, many college students will receive joint training of enterprises, and they will understand the characteristics and needs of the industry. We will also actively cooperate with professors in universities to jointly carry out research and development and accelerate the transformation of scientific and technological achievements. Domestically, we should establish a mechanism for jointly training students, joint research and development, and sharing of scientific research results, and jointly promote the cultivation of high-end talents and the production and research. Collaborate to advance the level of scientific research and clinical diagnosis and treatment."
In its view, companies should establish extensive cooperation with research institutes and medical institutions. Enterprises can use their technological advantages to help research institutes or medical institutions to establish technology platforms, to provide products and services to researchers with different interests and research directions, to maximize the application of new technologies and to promote their value.

" Single Cell Sequencing: Exploring a Window of Life "

A cell is the basic unit of the smallest structure and function of an organism. The DNA carries all the information that characterizes the living body except for other somatic mutations. In addition, the cell is also a vector unit for mutation and inheritance. Therefore, the most direct way to understand an organism and understand a life process is to study what happens at the single-cell level. He believes that single-cell sequencing is the ultimate in current life science research, and related research has a decisive role in promoting embryonic development and neurodevelopment. The main difficulty in sequencing single cells or a small number of cells is that the first step in sequencing requires first amplifying the sample. Once a minor error occurs in the replication, the error will be amplified during the next exponential replication process, eventually leading to We can't tell whether this error comes from a "copy" or a "mother".
MALBAC® technology uses a ring structure to lock the copy of the copy so that the copy cannot copy itself, and all copies can only come from the parent. After two years of continuous improvement in countless failures, the mature MALBAC® technology was finally developed. Compared with the traditional technology, the accuracy and coverage are much better, and the DNA detection coverage of tumor cells is as high as 93%. The usual technical means can only be 50%~70%. It is reported that Dr. Lu Sijia has successfully applied the technology to assisted reproduction, tumor research and other fields, and promoted the development and application of single-cell sequencing.

"From the laboratory to the clinic, all I did was to pursue the ultimate."

From scientific research to entrepreneurship, the application of scientific research results is the choice of many scientists. Dr. Lu Sijia said that the initial idea was to hope that his own achievements would contribute to the progress of human health, rather than just staying on paper. After the publication of the MALBAC® related article, the laboratory received a letter from a family member asking whether their research results would enable a healthy next generation of their families with hereditary multiple osteochondrosis. This opportunity touched Professor Xie and his team. They realized that their achievements could help China's vast genetic disease population. The landing of this technology will greatly improve the health and living standards of the next generation.
"I didn't expect to go from the laboratory to the clinical application so quickly. We have long predicted that this technology can be used in a lot of space, but we didn't think much about what we used. At that time, we just wanted to pursue the ultimate in science. Who is I didn't expect that MALBAC® technology would benefit patients so quickly,” Dr. Lu Sjia said with a smile.
In September 2014, the world's first MALBAC-PGDTM healthy baby was born, weighing 4030 grams and 53 cm in length. Subsequent umbilical cord blood genetic testing once again proved that the baby does not carry the pathogenic site of hereditary multiple osteochondroma. As of 2017, Yikang Gene successfully used this technology to successfully block more than 150 genetic diseases, and has helped more than 2,000 families to obtain healthy babies.

"" I have to "and" future "should pay close attention to the" future ""

Talking about the outstanding problems in the current industry, Dr. Lu Sijia pointed out that the first problem in China's genetic industry is that most enterprises are at the service end of the industry chain, that is, providing sequencing services. And a strong enterprise should go to the most upstream of the genetic industry, that is, the development and production of sequencing instruments, the development of new technologies for sequencing. From the perspective of a complete and healthy industrial chain, if Chinese companies do not have enough control over the upstream process of sequencing instrument production, the entire industry will be at risk. Because the entire domestic industry will be limited to foreign manufacturers, any commercial problems will bring irreparable losses to the domestic genetic industry. He stressed that the state should vigorously support powerful enterprises and lay a solid foundation for this part of the industry.
The second point lies in the clinical application, which is the most downstream of the entire industrial chain. He believes that except for NIPT, most clinical tests do not dare to claim that all aspects from technology to approval are mature; there are also many valuable technologies that have not landed, and do not reflect the value of technology in practical applications, nor for human health. The advancement of the cause plays its due role.
Faced with the problems existing in the upstream and downstream of the domestic genetic industry, Dr. Lu predicted that there should be a strong sequencer manufacturer in the future. At present, domestic enterprises have achieved initial results in related fields, and it is still to be seen who will dominate the future. Secondly, there will be good big data enterprises. The development of IT and Internet will promote the establishment of database of genetic industry, big data. Promoting scientific research and clinical development has become the new normal; finally, the gene sequencing service will be further subdivided, and provide patients with comprehensive, individualized diagnosis and treatment services before, during and after treatment.
In the past, present and foreseeable future, here is a blue ocean.
Transfer from - sequencing China

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