The core and clinical application transformation constraints of gene editing technology.

After experiencing the five revolutions of information technology, modern biotechnology has also ushered in an accelerated stage of leapfrogging, becoming another new revolutionary technology, is changing the world economic development model and the way of life of human society, and even in the future, human "old and sick" may show a different face.
in recent years, the gene editing technology represented by CRISPR technology undoubtedly occupies the "hot search" position.
7 years ago, CRISPR was rapidly applied to basic research, and today, through the continuous iteration optimization of scientists, gene editing technology in solving the major problems of human development, such as health, resources, environment and so on, showing broad prospects, leading to medical and agricultural changes. What is the core of
gene editing technology, why are people so fascinated by it, and what is constraining the transformation of gene editing technology and results into clinical applications? In this regard, the reporter and the Chinese Academy of Sciences, the Institute of Animal Research Director Zhou Qi held an exclusive dialogue.
the ory breakthrough and the application of innovation important field reporter: gene editing technology can be said to be very high, on your understanding, developed countries on the development of gene editing technology has taken a attitude? Zhou Qi: Gene editing technology, in layman's terms, is to accurately change the genome sequence through gene editing tools.
We all know that DNA is a double-chain structure, gene editing tools are like a pair of scissors, can accurately insert, delete, modify the target gene at a certain point in the chain, is a very broad application prospects of subversive technology, but in the process of application and development of the potential risks also caused a lot of controversy and discussion.
the United States and some developed countries in the United States and Europe have been leading in gene editing, especially in the development of source technology.
their government, science and technology community are highly concerned and invested in gene editing research and application, as a driving of major theoretical breakthroughs and application of innovation.
technology, the research focuses on developing new gene editing tools, improving gene editing efficiency, reducing off-target effects, and reducing the immunogenicity of gene editing tools.
at the application level, focusing on somatic gene therapy for major diseases, such as in 2016, the U.S. Food and Drug Administration (FDA) approved Sangamo's gene-editing therapy based on zinc finger ribucinase (ZFN) for the treatment of MPS I and haemophilia B; In February, the U.S. FDA approved for the first time a clinical trial of a new drug (IND) for Editas Medicine based on crispR gene editing edited EDIT-101, the world's first CRISPR drug to be approved by the FDA and conducted in clinical trials.
the American Academy of Sciences, the Royal Society and the Chinese Academy of Sciences jointly convened a summit on human gene editing in Washington, D.C., in December 2015.
the scientific community has reached a basic consensus on the application of gene editing technology, that is, the clinical application of gene editing in human reproductive systems is strictly prohibited at this stage, and basic research on gene editing and gene therapy at the stage of adult cells are encouraged.
February 2017, the United States has carefully opened up on the use of gene editing in human reproductive cells, in the face of a number of premises.
the National Academy of Sciences and the National Academy of Medicine's Human Gene Editing Board released a 261-page report, "Human Gene Editing: Science, Ethics, and Regulation."
report shows that gene editing techniques can be used to edit human eggs, sperm or embryos under strict supervision and risk assessment, but only when children with both parents who have severe genetic conditions and want to be healthy have no choice.
Reporter: For ordinary people, the more concern may be the impact of gene editing on life, can you talk specifically about what potential application innovations gene editing will drive? Zhou Qi: As an important platform technology, the application prospect of gene editing is very broad, for example, gene editing technology is the key core technology of gene therapy. many of the major genetic diseases caused by
genetic mutations are expected to be cured if the wrong DNA sequences are corrected at the genetic level through gene editing.
, scientists have successfully performed gene-edited gene therapy in animal models for many genetic disorders, including hyperemia, haemophilia, thalassemia, congenital black-mon, and Du's muscular dystrophy, which can effectively improve the condition.
in agricultural breeding, gene editing technology can more accurately and effectively improve the economic characteristics of crops and poultry and livestock, improve the resistance of crops and poultry livestock to viral infections, and thus promote the development of new varieties.
gene editing technology is also widely used in basic research, industrial production and biosecurity.
Clinical applications face many technical challenges Reporter: U.S. scientists recently announced the first gene editing technology to eliminate hiv in living mice, causing concern.
, do you think that such research results can speed up the application of the human body, China's research in this area of what progress? Zhou Qi: U.S. scientists report in Nature Communications on the complete elimination of HIV virus in humanized mouse models infected with HIV, and the innovation of this study is the combination of traditional antiretroviral therapy (ART) and gene editing techniques to achieve unexpected results.
such attempts can accelerate the clinical application of gene editing techniques.
China has laid out the research and application projects of gene editing in disease treatment in the science and technology special projects such as the national key research and development program, but in the reported clinical application of gene editing, the majority of clinical studies initiated by researchers are still in the majority, and the proportion of clinical trials for the purpose of drug declaration is less, so it still needs to be strengthened, which is very important to the development of gene therapy industry.
Reporter: People expect gene editing technology to eventually be applied to disease treatment, what is the biggest bottleneck to achieve clinical application? Zhou Qi: At present, the clinical transformation of gene editing has been tested in a few fields, such as beta-thalassemia, but gene editing therapy itself still has great technical challenges.
first of all, how to reduce the off-target effect of gene editing and thus prevent the risk of genomic non-targeted mutations. Secondly,
is how to improve the efficiency and safety of carrier delivery system.
currently, adenovirus-related virus (AAV) vectors are more widely used in clinical use because of their low immunogenicity, which allows them to have relatively high infection efficiency in the liver and improve the efficiency of the delivery system, but its infection capacity in other organs still needs to be improved.
at the same time, the current AAV capacity is too small and the efficiency of carrying gene editing tools into human cells is limited, so we need better delivery tools or smaller, more efficient gene editing tools.
gene editing ethics construction needs to attach great importance to the reporter: you proposed 3 years ago, China's gene editing technology also need to strengthen the layout, you think China should focus on what? Zhou Qi: In the research and application of gene editing technology, our government and industry have paid more and more attention to it, and many important progress has been made, which has laid a very solid foundation for the further development of gene editing research and application in China.
of course, we still need to pool the strength of gene editing technology, focusing on the original innovation of gene editing technology in the treatment of major diseases, gene editing technology research and application, as well as the establishment of gene editing animal and plant resource platform, and other objectives, to comprehensively enhance the research and development capability of gene editing technology in China, accelerate the application of gene editing technology in translational medicine and industrial and agricultural production, accelerate the application of scientific research results and related industries.
Reporter: In addition to the exploration you just said in the technical aspects, what breakthrough has been made in the construction of gene editing ethics in China? Zhou Qi: In the field of ethical construction, China has also issued relevant documents, such as the 2016 "Ethical Review Measures for Biomedical Research Involving Humans" and the 2018 Measures for the Management of Clinical Applications of Medical Technology, which explicitly prohibit the use of gene-edited human embryos for transplantation and generation; The genetic editing of human embryos of a research nature must be conducted in accordance with the "14-day" criterion, i.e. when conducting human embryonic stem cell research, the in vitro culture period of the germ made by in vitro fertilization, somatic cell nuclear transplantation, monosexual reproduction technology or genetic modification shall not exceed 14 days from the beginning of in vitro fertilization or nuclear transplantation.
, in addition, to carry out the necessary ethical review and comply with the principles of scientific integrity, informed consent, risk control, privacy protection and so on.
these principles are also current international consensus.
compared with developed countries, the construction of china's gene editing ethics system is still lagging behind, we still need to attach great importance to and increase efforts to improve legislation and build a regulatory system.
Reporter: How do you understand that you say that the construction of a genetic editing ethics system and improve the relevant regulatory system? Zhou Qi: In the supervision and ethical construction, at least four aspects of management need to be strengthened.
at present, the legal provisions related to human embryo gene editing are scattered in regulations and normative documents in multiple departments, the functions of the various regulatory authorities overlap, while the international technical developed countries are prescribed by special laws.
therefore, it is necessary to make special laws and regulations for the field of gene editing, and to clarify the functional boundaries between regulatory authorities in order to ensure the effectiveness of legal supervision.
also need to appropriately increase the penalties for violations of laws and regulations in the field of gene editing.
some of the current sectoral regulations or normative documents do not provide for punitive measures, or the punishment is far from sufficient, to a certain extent, weakenthed the effect of regulatory regulation.
foreign legislation, in the event of an act of artificially altering the genetic information of human reproductive cells for reproductive purposes, he could face up to five years in prison or a fine in Germany, and in France, 30 years in prison and a fine of 7.5 million euros.
second, a national-level unified ethics committee, or a number of regional ethics committees, should be set up to strengthen the review of similar ethically ground-breaking research and clinical applications.
In addition, in the field of life sciences and medicine, it is proposed to give full play to the autonomous role of the scientific community, and to formulate ethical norms and punishment measures that violate ethical principles through the scientific community in order to restrain the relevant acts of scientific researchers and medical personnel. At the same
time, government regulators should work with the scientific community to provide regular legal and regulatory and ethical training to enhance the self-discipline of researchers.
(originally published in Frontier Science, No. 3, 2019, with abridged content) Source: Frontier Science Science Daily.