On March 16th, Massachusetts General Hospital in the United States performed a special transplant surgery for a 62-year-old patient, transplanting a genetically edited pig kidney into their body to replace their own failing organ. Unlike the second patient in the world to receive a pig heart transplant in September 2023, who died of heart failure two months later, the pig kidney transplant patient has recovered well and has been discharged. Medical experts say that this genetically edited pig organ transplant program may bring hope to millions of kidney failure patients worldwide.

With the continuous advancement of genetic engineering technology, we are witnessing an unprecedented era. Scientists can more accurately edit the genes of living organisms using technologies such as CRISPR-Cas9, making the dream of precise gene therapy more and more accessible and changing fields such as industry, food, agriculture, health medicine, and biotechnology.

The genetically edited pig kidney can be transplanted to replace the failing human kidney. Visual China

Genetic engineering that rewrites the "code of life"

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The so-called gene is a DNA segment with genetic information, which is the complete sequence of nucleotides required to produce a polypeptide chain or functional RNA.

From 1856 to 1863, Austrian monk Mendel planted and tested about 5,000 pea plants and found that some traits of peas can be stably and regularly inherited by the next generation. The concept of "hereditary factors" he proposed was defined as "genes" by American scientist Morgan half a century later, establishing the theory of genetics. With the development of molecular genetics, Watson and Crick revealed the double helix molecular structure of DNA in 1953, allowing people to further understand the essence of genes.

"Genetic engineering, which includes gene editing, genetic engineering, recombinant DNA technology, molecular cloning, and gene cloning, is considered the core technology with the fastest development speed, the most innovative achievements, and the widest application prospects in biotechnology," said Zhu Jiankang, a member of the U.S. National Academy of Sciences and Dean of the Institute of Frontier Biotechnology Research at the Southern University of Science and Technology.

With the continuous deepening of genetic engineering research, people not only want to understand genes but also yearn to change them, in order to improve the yield of crops, improve the traits of living organisms, and even treat genetic defects.

According to Gu Ying, Deputy Dean of the Institute of Life Sciences at BGI, genetic engineering includes four basic elements: donor genes, recipient cells, tool enzymes, and vectors. It refers to the splicing and recombination of the target gene from a donor organism with a suitable vector outside the body, and then transferring it into another recipient organism, so that it can stably inherit and express the target gene according to the purpose of genetic engineering modification, such as improving the yield of livestock, aquaculture, and crops, and changing their appearance, body color, taste, and nutritional components and other traits.

Genetic engineering technology provides a powerful means for the study of gene structure and function, can cross the insurmountable gap between biological species, break through the species boundaries that are difficult to break through in conventional breeding, and has opened up a new field for transforming the genetic characteristics of organisms in a short period of time.Gene Editing: "Cut and Paste"

What is gene editing about? Gu Ying explains that this technology adjusts the function and expression of target genes by making precise insertions, deletions, or other types of mutations in the base sequence, thereby causing changes in the phenotypic traits of organisms.

For patients who have received gene-edited pig kidney transplants and recovered, their "life-saving kidneys" come from a miniature pig that has undergone multiple gene edits. These gene edits are designed to prevent the rejection of the donor organ (the key to the success of organ transplantation) and to reduce the risk of the patient being infected with hidden viruses in the pig's kidney after the transplant.

It is understood that scientists have modified 69 genetic loci of the organ donor pig using the CRISPR-Cas9 gene editing technique, including the knockout of three genes that produce three types of sugars on the surface of pig cells. The human immune system will attack cells carrying these three types of sugars and regard them as signs of foreign invaders. The other seven genes knocked in can produce proteins that prevent the pig's kidney from being rejected by the human body.

Gu Ying says that CRISPR-Cas9 is currently the hottest gene editing technology internationally and is a third-generation technology system. This technology can edit the genome by "cutting and pasting" DNA sequences, just like scissors, which can cut DNA at a designated location for gene editing.

At present, this technology has successfully achieved precise modification of the genomes of dozens of organisms such as fruit flies, rats, pigs, sheep, tilapia, rice, wheat, sorghum, etc. It has also shown great application prospects in the field of gene therapy for some diseases, such as blood diseases, tumors, and other genetic diseases.

Application Fields of Genetic Engineering

After the birth of genetic engineering, it was quickly applied to industries and fields such as industry, agriculture, medicine, food, and environmental protection, highlighting the great application prospects of this technology.

Gu Ying uses environmental protection as an example, saying that scientists have obtained bacteria with excellent decomposition and degradation capabilities through DNA recombination technology, which can greatly improve the degradation efficiency of plastics. In addition, scientists have also found bacteria that can degrade petroleum, pesticides, and insecticides through genetic engineering, which can be used for wastewater treatment in pesticide factories and chemical plants.

In the food industry, glutamic acid, flavorings, food colorants, and alcoholic beverages can all be produced through genetic engineering technology. For example, citric acid can be produced by genetically modified yeast and engineered bacteria. Not only that, but the yield of important food raw materials such as lactic acid, malic acid, threonine, and tryptophan produced by modified bacteria far exceeds the traditional methods.In the energy industry, the production of alcohol currently relies mainly on sugar crops and starch-based grains. Utilizing yeast and other genetically engineered strains can produce alcohol, and some super multifunctional bacteria can produce alcohol from straw, plant residues, and plant by-products, thereby increasing the yield.

In agricultural production, scientists have used genetic engineering technology to cultivate new varieties with excellent traits such as drought resistance, cold resistance, salt-alkali tolerance, and increased protein or oil content. Genetic engineering can also provide animal organs such as skin, cornea, heart, liver, and kidney that can be transplanted to humans, bringing hope to many critically ill patients.

In the field of health and medicine, genetically engineered drugs have always been a hot area of global research and development. Among them, bioactive peptide drugs are widely used in the treatment of cancer, hepatitis, malnutrition, diabetes, and other genetic diseases. Currently, more than 20 types of genetically engineered drugs have been approved for marketing in China, including interferons, recombinant human white blood cell interleukins, and recombinant human erythropoietin.

Genetic Engineering Biosafety Regulation

Experts believe that although genetic editing technology has a wide range of applications, it must be strictly regulated to prevent harm to human survival and national security.

Professor Wang Xu Chu from the School of Life Sciences at Guizhou University mentioned in "Genetic Engineering" that since genetic engineering is a new discipline and technology related to life, it is still in the stage of continuous development and improvement. Its safety for human health, ecological environment, and bioethics needs further evaluation. Genetic engineering technology itself should conduct research in the fields of biosafety of genetic engineering laboratories and biosafety of genetically engineered organisms, to answer and solve its own potential dangers to human health and the ecological environment.

Wang Xu Chu said that in the process of research and development and application of genetic engineering technology, it is necessary to strengthen its biosafety regulation, formulate relevant laws and regulations, establish a sound regulatory system, and carry out institutionalized supervision throughout the process. China attaches great importance to the supervision of biosafety of genetically engineered organisms, has established a relatively complete safety management system, institutions, testing and monitoring systems, and has issued a series of technical standards for the environmental and food safety evaluation and component determination of genetically engineered organisms. However, there is still a certain gap compared to the systematic supervision of European and American countries. It is necessary to fully learn from advanced experience and continuously improve China's regulatory system for biosafety of genetically engineered organisms, providing institutional guarantees for the widespread application of genetic engineering technology. Government departments should do a good job in publicizing and educating the public about the biosafety of genetically engineered organisms, guiding the public to understand genetic engineering and the huge benefits it brings to humans and the environment, avoiding the problem of "talking about transgenic color change", creating the correct social public opinion for the benign development of genetic engineering in China, and promoting the healthy and orderly development of related industries.

Shenzhen Competes in the New Track of Cell and Gene Industry

Strive to develop into a strategic emerging industry within 5-10 years.

Develop future drugs based on DNA. Visual ChinaNot long ago, Shenzhen City's "20+8" second batch of industrial funds determined the "housekeeper", among which Shenzhen Songhe International Capital Management Partnership Enterprise was selected for a 1.5 billion yuan cell and gene industry fund, mainly investing in cell and gene therapy, new viral vectors, new vaccine research and development, gene technology, biological breeding and other fields. This move will accelerate the deep integration of the cell and gene innovation chain industry chain, and empower the high-quality development of future industries.

The cell and gene industry has become one of the most important fields in the forefront of global biomedicine and life science exploration, and is a new driving force for future industrial growth. Shenzhen is actively deploying this new field and new track, listing the cell and gene industry as a key future industry for cultivation and development, and striving to develop into a strategic emerging industry within 5 to 10 years.

On March 1 last year, the "Shenzhen Special Economic Zone Cell and Gene Industry Promotion Regulations" came into effect, which is the first special legislation on the cell and gene industry in the country, showing Shenzhen's determination to seize this track. The "Regulations" focus on the promotion and support of the cell and gene industry, and further require and deploy the government management regulations, technical specifications, production quality management specifications, and policy support for the processes such as cell collection and storage, cell and gene product research and development, drug expansion clinical trials, gene technology application, marketing authorization, and product production, to escort Shenzhen's cell and gene industry into a new stage of rapid development.

In fact, as one of the earliest cities in the country to deploy the development of the cell and gene therapy industry, Shenzhen has always attached great importance to basic scientific research and industrial development in the field of cells and genes, and has a "first-mover advantage".

As early as 2013, Shenzhen formulated and issued the "Ten-Year Development Plan for the Life and Health Industry", listing cell and gene therapy technology as a future industry for cultivation, and took the lead in deploying related facilities for industrial development across the country, relying on BGI to build the Shenzhen National Gene Bank, relying on Beike Biology to build the Shenzhen Comprehensive Cell Bank, and initially forming a leading innovation of leading enterprises, and the development of small and medium-sized enterprises, the industry is in the expansion period.

In 2022, the "Shenzhen Science and Technology Innovation '14th Five-Year Plan'" was introduced, and cells and genes were listed as one of the eight future industries in Shenzhen, proposing to strengthen frontier technology research and technology application, break through a number of key core technologies, frontier leading technologies, and disruptive technologies, promote the industrialization of a number of major scientific and technological achievements, and create new growth points for industrial development.

In June of the same year, the "Shenzhen Action Plan for Cultivating and Developing Future Industries (2022-2025)" was released, which clearly stated that the cell and gene industry focuses on the development of cell technology, gene technology, cell and gene therapy technology, and biological breeding technology, striving to achieve exponential growth within 5 to 10 years.

With the support of a series of policies, the development momentum of Shenzhen's cell and gene industry is strong, with a number of innovative enterprises, research institutions, and major platforms with core technologies such as BGI Group, Beike Biology, Haplos, Saidong Intelligent Manufacturing, Shenzhen Kono Medical Laboratory, Chinese Academy of Agricultural Sciences Shenzhen Agricultural Genome Institute, and National Engineering Research Center for Key Common Technologies of Cell Industry, which have rapidly developed and built an industrial chain from basic research, gene sequencing, cell storage, cell preparation, to product research and development, clinical trials, and quality testing.

Chinese Academy of Agricultural Sciences Shenzhen Agricultural Genome Institute: Breakthroughs in Multiple Gene Biological Research

Recently, the Chinese Academy of Agricultural Sciences Shenzhen Agricultural Genome Institute (referred to as "Genome Institute") has achieved a number of significant research results in the fields of biological breeding and food safety, including genomics, important functional gene analysis, gene editing breeding, and synthetic biology.On January 26th of this year, "Science" published the latest research achievement "Identification and Heterologous Reconstruction of Bacatine III Biosynthetic Enzymes" led by the team of Yan Jianbin, a researcher at the Genome Institute. The study successfully identified the key missing enzyme in the biosynthesis pathway of paclitaxel, revealed the enzymatic mechanism of plant cells catalyzing the formation of oxetane structures, and established the shortest biosynthesis pathway for paclitaxel to date, which is expected to solve the problem of insufficient supply of the "star anti-cancer drug" paclitaxel.

Recently, the Genome Institute has mapped the continuous reference genome from telomere to telomere of the small liverwort, annotated the new reference genome de novo, and proved that the chromosome number of the small liverwort is 26, with an accuracy rate of 99.9989% after assessment. This study has laid a genetic foundation for the heterologous synthesis of important natural products such as paclitaxel using the small liverwort as a chassis.

Not long ago, the green and simple super rice genetic analysis and molecular breeding innovation team of the Genome Institute identified the key protein causing wheat head blight, deepening the understanding of the occurrence mechanism of wheat head blight. The study found that the Fusarium graminearum causing wheat head blight secretes a type of subtilisin protease, which leads to non-specific plant cell death. After knocking out this gene, the pathogenicity of the pathogen was significantly reduced, and the toxin content in the wheat ear was reduced.

In addition, the Genome Institute used global micro-core germplasm resources to construct the population expression profile of rice under salt stress, and analyzed the impact of gene expression on phenotype under salt stress from a whole-genome level. The study found that the dynamic changes in gene expression led to differences in the salt tolerance of the population, and a key excellent allele for salt tolerance was identified. This study provides important resources for the excavation of excellent salt-tolerant genes and the cultivation of salt-tolerant rice.

Shenzhen National Gene Bank: Can store tens of millions of biological samples

Can store tens of millions of biological samples; Pb-level gene data output center; Archive more than 13PB multi-omics data, support data exchange and sharing of more than 500 global units; Release 90 standards... Located in the Dapeng New District, the Shenzhen National Gene Bank has been in operation for 8 years, creating a "two libraries and one platform" to achieve an organic linkage of "storage, reading, and use" of biological resources and information, playing an important role in the major scientific and technological infrastructure, and making a positive contribution to promoting the progress of life sciences and the development of the bioeconomy in our country.

It is reported that the Shenzhen National Gene Bank consists of a biological sample library, a biological information database, and a digital platform. Among them, the biological sample library is an important means to protect the safety of national biological resources and human genetic resources, and to avoid potential biological threats. There are multiple temperature layers such as 4°C, -20°C, -80°C, and -196°C liquid nitrogen. The biological sample library stores biological resources, the digital platform reads the genetic data of organisms with sequencers, then the biological information database stores these data, or uses supercomputers for analysis and calculation, and finally serves the research and development of life sciences and the bioeconomy.

"Preserving, protecting, and making good use of genetic resources has become a solid foundation and effective guarantee for international competition and major needs of a healthy China, and the development and utilization of genetic resources will occupy the commanding heights of the global bio-industry chain in the future." said the person in charge of the Shenzhen National Gene Bank.

"Shenzhen-made" sequencer: Helps restore the appearance of Emperor Wu of the Northern Zhou Dynasty

A few days ago, the Shaanxi Provincial Institute of Archaeology released the archaeological findings and research results of the tomb of Emperor Wu of the Northern Zhou Dynasty, Yuwen Yong, and the tomb of the founding emperor of the Northern Zhou Dynasty, Yuwen Jue, and also preliminarily restored Yuwen Yong's appearance in a scientific archaeological manner. It is reported that the scientific research team used a gene sequencer made by Shenzhen BGI to help restore the appearance of Emperor Wu of the Northern Zhou Dynasty.Extracting DNA from a large cemetery and successfully completing subsequent sequencing and analysis is quite challenging. In September 2023, the research team, combining the excellent performance of the DNBSEQ-G99 gene sequencer from BGI Tech in terms of endogenous rate and library complexity, obtained about 1 million usable genetic loci from the limb bone samples of Emperor Wu of the Northern Zhou. This result enabled the team to successfully obtain loci related to pigment deposition for the reconstruction of Emperor Wu's appearance and loci related to disease inference, and further conducted a more refined quantitative analysis of Emperor Wu's ethnic origin.

On this basis, the research team combined skull CT scanning technology to preliminarily restore Emperor Wu's appearance and analyzed genetic loci related to hair, skin, and pupil pigment, performing a "facial reconstruction" that spanned a thousand years for Emperor Wu. The reconstruction results show that Emperor Wu of the Northern Zhou, Yuwen Yong, had black hair, yellow skin, and brown eyes, which are consistent with the typical appearance of Northeast Asian and East Asian people, and are very different from the imagined Xianbei ethnic appearance with strong exotic characteristics - lush beard and hair, yellowish hair color, and high nose and deep eyes.