From gene editing to xenotransplantation The underlying problems of biotechnology innovation have yet to be solved

Gene editing technology has been surprising to mankind in recent years, and it has become a key technology supporting many advanced therapies such as organ transplantation and cell therapy.

As a source of the next generation of biotechnology revolutions, the researchers believe that gene-editing technologies will enable amazing innovations in medicine, agriculture, and many other fields, but the associated ethical challenges and technological innovations still need to be broken.

The underlying technological innovation needs to be broken

The world's first patient with a heart xenotransplantation survived two months after receiving a heart from a genetically modified pig, a miracle in medical history. Using the gene-editing technology CRISPR–Cas9, U.S. researchers transplanted ten genetically modified pig organs into humans for the first time, and the results suggest that the method worked at least for a while.

Last month, a U.S. research team claimed to have cured a female AIDS patient for the first time using a cutting-edge stem cell transplant method. Along these lines, the researchers hope to use genetic modification to find a cure for AIDS and eradicate the virus once and for all.

Crispr-Cas9, the earliest gene editing technology based on bacterial immune mechanisms, has shown great potential in human drug therapy, and has now become the basis for the treatment of genetic diseases such as sickle cell anemia, and will provide precision treatment programs for more diseases in the future.

The mainland attaches great importance to the research and development of gene editing, and has listed it as a key research target in the "14th Five-Year Plan" period. In January this year, the state issued safety management specifications for gene editing products, paving the way for promoting gene editing applications.

At this year's two sessions, how to achieve the underlying innovation breakthrough of gene editing technology has attracted the attention of members from the Chinese Academy of Sciences.

Cao Xiaofeng, member of the National Committee of the Chinese People's Political Consultative Conference, academician of the Chinese Academy of Sciences, and researcher of the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, said: "Although the mainland is at the forefront of the world in the research and development and application of animal and plant gene editing technology, the original patents are seriously lacking, the core patents and underlying technologies are mostly monopolized by western countries led by the United States, and industrial security is facing serious challenges. ”

Cao Xiaofeng said that gene editing is developing rapidly in two aspects: in terms of basic research, including the mechanism research of gene editing tools, model establishment, original innovation research and development, and the optimization of existing editing tools; in terms of technology application, accelerate the transformation and application of research results, achieve a deeper technological leap, promote industrial landing, and build a bioeconomy with gene editing technology as the pillar.

At present, many units in the mainland are accelerating the establishment of gene editing technology centers and laboratories, and promoting the industrialization of gene editing technology in the mainland into the fast lane. However, Cao Xiaofeng believes that most of the layout of the domestic gene editing field focuses on product-driven technology research and development and transformation applications, and lacks basic research on gene editing tools and original innovation in underlying technologies, making it difficult to completely reverse the passive situation in which core technology and industrial development are subject to people.

In this regard, she suggested strengthening the strategic scientific and technological strength in the field of gene editing, building a "gene editing basic discipline research center", increasing capital investment in basic research; focusing on multiple research and application dimensions such as animals and plants, microorganisms, major diseases and modern agriculture, and deeply carrying out research on gene editing molecular mechanisms, programmable nuclease structure analysis, new tool mining, delivery and editing new technology research and development; promoting the output of original and subversive basic research results, and accelerating the transformation of research achievements and the industrialization of technology.

Ethical regulations need to be improved

At the same time, the scientific community and global governments are still exploring and seeking solutions on how to use innovative biotechnology for the benefit of humanity within an ethical framework. In the process, some radical attempts have also been called into question.

For example, He Jiankui, a former professor at Southern University of Science and Technology in China, used gene editing technology to gene edit the fetuses of AIDS patients. However, this adventurous behavior has aroused great controversy in the world's scientific community due to ethical controversies and forged experimental ethics approval procedures.

But that still can't stop the wheels of scientific progress. In April last year, Chinese researchers published a blockbuster paper in the journal Cell, which for the first time creatively injected human stem cells into the embryos of non-human primate crab-eating monkeys, and the proportion of human cells reached expectations, and the human-monkey chimeric embryos survived for nearly 20 days. This achievement announced a major breakthrough in the research of chimeric embryos in human monkeys, and the cultivation of stem cells in vitro organs went one step further.

In the longer term, the researchers also hope to use these chimeras to study early human development, develop disease models, screen for potential new drugs, and make cells, tissues, or organs that can be transplanted, and one day create new hearts and kidneys to save patients who need to be transplanted.

Professor Ji Weizhi, an academician of the Chinese Academy of Sciences and the Institute of Primate Translational Medicine of Kunming University of Science and Technology, who is responsible for the above research, believes that biotechnology, including gene editing and gene fusion, still needs to make breakthroughs in ethics and innovation.

Taking xenotransplantation as an example, Ji Weizhi told the first financial reporter: "Ethically there should be regulations related to xenotransplantation, and technically it is necessary to improve the survival rate of xenotransplantation and reduce immune rejection." ”

He believes that xenotransplantation may also be realized in China in the future, and some restrictions on research ethics will be revised to adapt to the development of science.

Professor Wu Zhongjun, director of the Artificial Organ Laboratory at the University of Maryland, told the first financial reporter that there are still many unknowns about xenotransplantation, such as immunosuppressive therapy. But he said: "In any case, we have learned a lot from this case and will definitely apply what we have learned to future research." ”

"Technology itself is free of good or evil, and in the field of medical health, before a new therapy is put into use, the first thing we have to consider is safety, and then effectiveness." Mao Mao, founder and CEO of Siqin Medical, told the first financial reporter, "In addition, before the new therapy is used in people, it is necessary to do a large number of in vitro tests, know its role, and then do in vivo tests; and should first start from the so-called 'ultimate patient', rather than first apply from the perspective of prevention, this pig heart transplant is a good example." ”

As one of the experts who participated in the review of the first edition of the Genetic Resources Management Measures in the 1990s, Mao Mao believes that gene editing technology is a good field for the treatment of genetic diseases, and some treatment of acquired diseases can be done in the future.

Some places have begun to ease access restrictions to innovative healthcare markets and support advanced therapies such as stem cells. In January this year, Shenzhen issued the Opinions on Several Special Measures for Shenzhen to Build a Pioneering Demonstration Zone of Socialism with Chinese Characteristics to Relax Market Access, which specifically mentioned the optimization of human genetic resources approval and access services, and supported the research and development of new medical products and technologies such as stem cell therapy, immunotherapy, and gene therapy.