The world's first successful transplantation of a gene-edited pig lung into a human body. Interview with the main participants: How far is it from clinical application?

One year after the project was launched, on the evening of August 25th, the news that a Chinese research team had successfully transplanted a gene - edited pig lung into a human body went viral. He Jianxing, a professor at the National Center for Respiratory Medicine of the First Affiliated Hospital of Guangzhou Medical University, and his collaborators found that a genetically engineered pig lung could survive and function for 9 days after being transplanted into a human patient diagnosed with brain death.

Due to the shortage of lung donors, many patients with end - stage organ failure lose hope while waiting. This breakthrough has shown the industry the possibility of moving xenogeneic lung transplantation from the laboratory to the clinic. What is the significance of this research for the dilemma of donor shortage in lung transplantation? How far is it from clinical application?

In this regard, a reporter from National Business Daily interviewed Chen Zhonghua, one of the authors of the paper and an authoritative expert in the field of organ transplantation in China, and Pan Dengke, the founder of Chengdu Zhongke Aoge Biotechnology Co., Ltd., the developer of the experimental donor pigs, and other major participants at the first time.

"Previously, humans have tried pig heart and pig kidney transplants, but this is the first successful connection of a pig lung, which makes the scientific community feel that it has taken a big step forward," explained the relevant person in charge of Yunzhou Biotech, a gene delivery outsourcing company, to the reporter. The lung is considered the "most difficult" organ to transplant. Professor He's research is the world's first to transplant a pig lung into a human body, so it is regarded as a milestone event.

Pan Dengke, the developer of the donor pigs, told the reporter from National Business Daily that to achieve better survival results, it is necessary to optimize the preparation plan of donor pigs in a targeted manner. Zhongke Aoge is accelerating the research and development of various types of compatible pigs. Continuously optimizing the immunosuppressive regimen means that more pre - clinical and clinical data need to be accumulated.

Key Breakthrough: The First Record of Cross - Species Lung Transplantation

"We adhere to the principle of not releasing news but only scientific papers. Top - tier journals also have a similar 'Embargo System' when pre - reviewing important manuscripts to ensure the maximization of scientific value and influence at the time of publication," said Chen Zhonghua, an authoritative expert in the field of organ transplantation in China.

On the evening of August 25th, the paper "Successful Transplantation of a Gene - Edited Pig Lung into a Human Body" with He Jianxing, a professor at the National Center for Respiratory Medicine of the First Affiliated Hospital of Guangzhou Medical University, as the first author and Chen Zhonghua and other industry experts participating, was published in Nature Medicine. Meanwhile, Science specially issued a news release about this paper.

Xenotransplantation refers to the transplantation of an organ from one species into another. The world's first xenotransplantation surgery can be traced back to 1906, earlier than human allogeneic organ transplantation. However, due to problems such as rejection reactions, its clinical application has been far behind allogeneic organ transplantation.

The reporter from National Business Daily noticed that the paper titled "A Case of Porcine - to - Human Lung Xenotransplantation" detailed the process of this cross - species lung transplantation. The research team transplanted the left lung of a six - gene - edited (GTKO/B4GalNT2KO/CMAHKO/CD55/CD46/TBM) Chinese Bama miniature pig into a 39 - year - old male recipient who had suffered a brain death due to a cerebral hemorrhage. The total cold ischemia time of the donor lung from retrieval to reperfusion was 206 minutes, and the experiment was terminated on the 9th day (216 hours) after the surgery.

During the 216 - hour monitoring period, the lung xenograft remained viable and functional, with no signs of hyperacute rejection or infection. This indicates that hyperacute rejection can be avoided through gene editing and corresponding immunosuppressive regimens.

Twenty - four hours after transplantation, the team observed severe edema similar to primary graft dysfunction, which may have been caused by ischemia - reperfusion injury. On the 3rd and 6th days after the surgery, antibody - mediated rejection seemed to cause damage to the xenograft, and partial recovery was observed on the 9th day.

The paper also mentioned that although this study demonstrated the feasibility of porcine - to - human lung xenotransplantation, significant challenges related to organ rejection and infection still exist. Continuous efforts are needed to optimize the immunosuppressive regimen, improve gene modification, refine lung preservation strategies, and evaluate the long - term graft function after the acute phase. By addressing these challenges, future research can improve the method of lung xenotransplantation and bring it closer to clinical translation.

Lung transplantation is currently the only way to truly replace the lungs, mainly used for patients with end - stage lung diseases. One of the main reasons is the shortage of available lung donors. Another reason is that the lungs have a large surface area and are particularly fragile when inflated. This makes the lungs easily damaged during the retrieval and transplantation process, so the success rate of lung transplantation is relatively low among all organ transplants.

Even allogeneic transplantation faces such difficulties, and xenotransplantation faces even greater challenges. When organs are transplanted between different species, the human immune system will regard the foreign organ as an "invader," and the rejection reaction will be particularly strong.

Pan Dengke said that whether it is allogeneic or xenogeneic transplantation, lung transplantation faces much greater obstacles than other solid organ transplants. These challenges include strong immune rejection reactions, high sensitivity to ischemia - reperfusion injury, complex organ compatibility issues, and an increased risk of infection due to direct exposure to the external environment.

Therefore, before transplantation, the organs of the donor pigs need to be genetically modified to solve the problem of immune rejection. Simply put, it is to modify the genes of pigs through technical means so that the human immune system "cannot recognize" that it is a pig's organ.

The relevant person in charge of Yunzhou Biotech explained to the reporter from National Business Daily that Professor He's team used a gene - edited pig lung as a donor, deleting three carbohydrate molecules that are most likely to trigger human immune rejection and adding three protective human - derived proteins to reduce complement attack and abnormal blood coagulation.

Source of the picture of the experimental pig: Provided by Zhongke Aoge

"Simply put, it's like giving the pig lung a 'big makeover'. Remove the parts that may cause 'strong allergic reactions' in the human body and install 'human parts' for compatibility. Doctors first installed it in a patient who had suffered a brain death for testing. The pig lung could work for a period of time, but some rejection reactions still occurred," the above - mentioned relevant person in charge further said. Previously, humans have tried pig heart and pig kidney transplants, and the lung is generally recognized as the most difficult organ in the industry, so this research is regarded as a milestone.

The research case shows that the gene - edited pig lung can remain viable and functional without hyperacute rejection. However, the observed complications also indicate that although these results provide valuable mechanistic insights into the human immune response to xenogeneic lungs, the road to clinical application of lung xenotransplantation is much more difficult than that of other organs (such as the kidneys).

The aforementioned relevant person from Yunzhou Biotech also said that simply put, this experiment proved that the pig lung "can survive," but it's like a "prototype" test, and it's still a long way from being used on living people. In the future, it is necessary to prove that: the pig lung can support human breathing alone for several weeks or even months; the amount of medication cannot be so large that it completely destroys human immunity; and it cannot bring the risk of pig viruses.

When interviewed by the media, He Jianxing said that this achievement marks a key step in the field of xenogeneic lung transplantation. Next, the gene - editing strategy and anti - rejection treatment regimen will be further optimized to prolong the survival time and functional maintenance of the transplanted organ. The tubeless technology independently developed by the team will also be applied to xenogeneic lung transplantation experiments to reduce the damage of mechanical ventilation to the donor lung and promote the clinical translation of lung xenotransplantation.

Lung Donor Demand: How Far is Xenotransplantation from Clinical Application?

"Although human organs are the most suitable, their quantity is far from meeting the demand," said Chen Zhonghua, the first person in China to practice the theory of international standardized organ donation, who has a clear understanding of the current shortage of transplant organs.

He told the reporter that based on the number of registered wait - list patients, the supply - to - demand ratio of organs available for transplantation in China in 2024 was approximately 1:8. However, the actual situation is much more serious because many potential wait - list patients are not included in the list due to their inability to afford the relevant costs.

Abroad, exploring new sources of organs is also an important topic in the field of organ transplantation. Chen Zhonghua said that an ideal organ source should meet three conditions: high accessibility, being available at any time when needed; relatively low cost, being affordable for patients; and transplantation results that are not much different from allogeneic organ transplantation.

The academic community has been looking for ideal xenogeneic organs. Previous studies have shown that since pig organs are similar in size to human organs and their sources are unrestricted, transplanting pig lungs instead of human donor lungs to patients is a good choice, which can effectively relieve the problem of donor shortage. Moreover, gene modification has effectively reduced the immunogenicity of pig donor lungs.

In recent years, a series of remarkable breakthroughs have been made in the field of xenotransplantation. In October 2021, the Langone Medical Center at New York University transplanted a gene - edited pig kidney into a brain - dead woman for the first time. In January 2022, the University of Maryland School of Medicine performed the first surgery to transplant a gene - edited pig heart into a living person, and the patient survived for about 2 months after the transplantation.

In March 2025, the team led by Academician Dou Kefeng of Xijing Hospital of the Air Force Military Medical University published a paper in the journal Nature, reporting the first transplantation of a gene - edited pig liver into a brain - dead patient. The organ survived and functioned normally in the brain - dead patient for 10 days.

The picture of Zhongke Aoge's donor pigs published in Science. Source: Provided by Zhongke Aoge

These breakthroughs have attracted wide attention worldwide.

However, Chen Zhonghua told the reporter that the research on pig lung transplantation surgery is an original first - of - its - kind study with many highlights, but it cannot solve the difficulties of applying lung transplantation in the clinic. In his view, xenogeneic lung transplantation is still very far from clinical application. "According to the basic requirements, relevant research in primates needs to achieve 5 to 6 consecutive cases of subjects surviving for more than half a year before basic clinical research can be carried out. Currently, no domestic team has reached the standard for conducting clinical trials."

Zhong Hao, the chairman of Dashuo Group, who is involved in the preparation of donor pigs, is relatively more optimistic about this cutting - edge technology. He told the reporter that gene - editing technology not only involves the modification of short sequences but also the precise manipulation of genes with super - large fragments of more than 500 kb (kilobase pairs). The knock - in, integration, and subsequent stable expression of such large fragments are recognized technical difficulties.

"The technical difficulties of xenotransplantation have been overcome. It can even be said that it is no longer a technical problem for the survival time of xenotransplantation to exceed that of allogeneic transplantation (referring to human organ transplantation)," but Zhong Hao also mentioned that from application in brain - dead patients to end - stage patients and then to clinical trials with statistical significance, xenotransplantation still needs to accumulate more cases.

He predicted that if at the fastest speed, there will be enough clinical cases to submit a clinical trial application next year, and xenotransplantation is expected to make a major breakthrough in the next 5 years.

The reporter also noticed that as a cutting - edge biomedical technology, there is currently no available regulatory mechanism for xenotransplantation. Relevant departments need to clarify ethical norms and technical requirements. At the enterprise level, it is necessary to further optimize the preparation plan of donor pigs and improve the quality management system.

Gene - Edited Pigs: Putting China at the Forefront of the "Global Competition" in Xenotransplantation

It is understood that for xenotransplantation to make a major breakthrough, the first step is to use gene - editing technology to create donor pigs that meet the requirements of xenotransplantation.

Among them, gene - editing technology is mainly used to obtain donor pigs with ideal genotypes. To achieve this goal, extremely high requirements are placed on the precision and manipulation scope of gene - editing technology.

"Gene - editing technology can be said to be the 'pearl on the crown' of science. Previously, the gene - editing technology used could even achieve 64 - gene editing, but in fact, more editing is not always better because at that time, it was not certain which genes needed to be knocked out and inserted," Zhong Hao said. The six - gene - edited pigs of Zhongke Aoge are basically on par with the current international advanced level.

Source: Provided by Zhongke Aoge

The second step is to breed the donor pigs created by gene - editing technology in a DPF facility.

This requirement is due to the fact that in xenogeneic organ transplantation, the risk of cross - species infectious diseases is fatal. Previously, Bennett, an American man who was the world's first recipient of a pig heart transplant, died for unknown reasons after the surgery. Later, researchers found that the donor pig heart was latent with porcine cytomegalovirus (PCMV), which is also speculated to be the possible cause of Bennett's death. The DPF sterile pigs prepared and bred through ultra - clean technology can help overcome this problem of pathogen - microorganism control.

Pan Dengke also said that the technical advantage of Zhongke Aoge lies in that the donor pigs modified by gene - editing means can not only achieve high expression but also natural breeding and stable inheritance, which is more feasible for industrial transformation.

It is understood that with the technological breakthroughs in xenotransplantation, Zhongke Aoge and Dashuo Group, two high - tech companies in Chengdu, have continuously helped Chinese scientists stay at the forefront of the world in the field of xenotransplantation. Since this year, Zhongke Aoge has participated in 3 important xenotransplantation surgeries, namely, the xenotransplantation in a brain - dead recipient in January, the xenotransplantation in a patient with end - stage renal disease in March, and the current pig lung transplantation surgery.

Pan Dengke said that the research in January was the world's first in - situ liver transplantation from a pig kidney to a brain - dead human. Like this (lung transplantation), it was an exploratory sub - clinical study, mainly aiming to observe the feasibility of pig - to - human organ transplantation, especially to preliminarily verify the safety and effectiveness of gene - edited pigs.

"The pig kidney transplantation in March was a breakthrough clinical treatment. Currently, the patient has been under post - operative observation for nearly 6 months and is in good condition. Judging from the accumulation of experimental data, xenogeneic kidney transplantation should still be the first pipeline to enter clinical translation. The FDA (US Food and Drug Administration) also approved clinical trials for kidney transplantation first," Pan Dengke added.

Regarding the next research plan, Pan Dengke revealed that there are a total of 26 pig - to - human sub - clinical and clinical studies being carried out globally, and Zhongke Aoge has participated in 10 of them. The first transformation pipeline is xenogeneic kidney transplantation, and the time to promote clinical trials depends on the establishment of a xenotransplantation regulatory mechanism. In addition, the company