EdiGene CEO Wei Dong Advocates Differential Regulation of Somatic vs. Germline Gene Editing in IPO Prospectus

Gene Editing: Technologies including CRISPR, TALEN, and ZFN employ molecular biology methods to edit target genes, enabling the trimming, cleavage, replacement, or addition of specific DNA or RNA sequences.

Gene editing technology has been hailed by the scientific community as a revolutionary advancement in modern medicine. It makes it possible to cure certain chronic diseases—currently incurable by existing medical interventions—with a single treatment. “However, this ‘one-time’ nature is also a double-edged sword; any therapeutic errors or adverse reactions could cause lifelong harm to patients,” stated Dr. Wei Dong, CEO of Boya Ji Yin (Beijing) Biotechnology Co., Ltd. Therefore, the application of gene-editing therapies must be approached with exceptional rigor and caution.

The 2018 He Jiankui gene-edited baby incident shocked the world. Scientists both domestically and internationally spoke out, expressing their anger and condemnation of the event.

On March 14 this year, 18 scientists and ethicists from seven countries around the world jointly published an article in the top academic journal *Nature*, calling for a global moratorium on all clinical research involving human germline gene editing and the establishment of an international regulatory framework.

These 18 scientists and ethicists all hail from top-tier institutions worldwide. Among them is Professor Wei Wensheng, a researcher at the School of Life Sciences, Peking University, and founder of Boya Ji Yin.

On April 24, following a joint publication in Nature by 18 prominent scientists and ethicists in the field of gene editing calling for action, 62 scientists once again wrote to the U.S. Department of Health and Human Services, urging a global moratorium on the clinical application of germline gene editing.

Boya JiYin CEO Wei Dong (Photo provided by the interviewee)

As one of the revolutionary technologies in modern medicine, why has the clinical application of gene editing in human germ cells been collectively halted by scientists? What is the positive direction for the development of gene editing technology? VCBeat reporter conducted an exclusive interview with Dr. Wei Dong, CEO of Boya Jiyin.

“Gene editing therapies actually fall into two categories: one involves editing patients’ somatic cells to treat diseases, while the other entails editing germ cells (i.e., sperm, oocytes, or zygotes) with the aim of preventing certain genetic disorders or enhancing specific traits. The implications of these two approaches differ drastically.” Dr. Wei Dong stated that following the He Jiankui incident, they observed that foreign media and regulatory authorities clearly distinguished between somatic cell editing therapies and germ cell editing. In contrast, domestic discourse rarely draws a strict distinction between these two concepts, often employing the broad term “gene editing,” which has, to some extent, misled public understanding of this technology.

“I strongly endorse NPR’s characterization of these two concepts: in the context of disease treatment based on somatic cell gene editing, only the DNA of the individual patient is altered. This form of gene editing does not carry the risk of altering the human species. Furthermore, such treatments are underpinned by extensive and rigorous scientific research, thereby minimizing potential adverse outcomes. In stark contrast, He Jiankui’s research involved germline editing. The modifications he made can be inherited across generations. Moreover, germline editing capable of altering heritable traits has been halted, and its safety has not yet been confirmed by the majority of scientists.”

Photo provided by the interviewee

Dr. Wei Dong introduced that somatic cell gene editing therapy involves using gene editing technologies to edit differentiated or directionally differentiating somatic cells from patients or donors, with the aim of treating diseases in individuals who are already born, suffering from a specific condition, and for whom existing therapies cannot adequately improve their symptoms. The benefits and risks of such therapies are confined to the individual patient and are not inherited by subsequent generations.

Taking the ex vivo gene-editing therapy for patients with severe β-thalassemia currently under development by Boya JiYin as an example, its principle involves extracting the patient’s own hematopoietic cells, editing a specific gene using technical methods, and then transplanting the modified cells back into the patient. This enables the erythrocytes differentiated from these cells to express hemoglobin at near-normal levels, thereby achieving therapeutic efficacy. In-depth scientific research and sophisticated manufacturing processes can significantly reduce associated risks. Even in the unlikely event of unforeseen errors, patients can undergo a second transplantation. Therefore, the risks associated with this type of therapy are relatively manageable.

Currently, somatic cell gene editing technology has accumulated extensive and in-depth scientific research achievements worldwide. In the United States, Europe, and China, multiple therapeutic projects targeting cancer, genetic disorders, and HIV/AIDS have entered clinical stages, whereas human germline cell editing technologies remain relatively limited.

In 2015, researchers at Sun Yat-sen University used CRISPR/Cas9 technology for the first time to modify genes in human embryos that could lead to thalassemia, and published their findings in the medical academic journal *Protein & Cell*. Unlike the He Jiankui incident, the Sun Yat-sen University researchers used problematic embryos discarded by hospitals, which would not have developed into infants.

In accordance with international conventions, the application process for innovative drugs or technologies typically begins with trials in patients with the most severe conditions, as they stand to gain benefits that outweigh the risks. Following successful trials and an enhanced understanding of associated risks, researchers can then evaluate the risk–benefit profile for patients with milder conditions, cautiously extending applications to those with moderate disease severity and early-stage conditions. Only thereafter will consideration be given to applying these innovations to specific patient populations, such as pregnant women. Scientists often need to steadily establish a scientific risk assessment framework for any innovative drug or technology through long-term clinical adoption and data accumulation.

“Although a certain amount of data has been accumulated from animal studies, germ cell gene editing technology is still a long way from clinical application, with many unknown risks in between,” said Dr. Wei Dong. He explained that the reason the He Jiankui incident drew unanimous condemnation from industry insiders was that he directly applied a very new technology in a context of extremely high and unassessable risk. This approach is completely contrary to the spirit of science.

Another issue with this practice, as noted by Dr. Wei Dong, is that from a genetic perspective, the two infants who underwent germline gene editing were only at risk because their father was infected with HIV; their own likelihood of infection was extremely low, and highly effective methods already exist to prevent transmission either before or after birth. Replacing an existing intervention with well-characterized and minimal risks with one carrying unknown risks is highly undesirable from both scientific and ethical standpoints.

In February this year, Boya Jiyin secured a RMB 70 million Pre-B+ financing round led by Sinopharm Capital, marking another significant funding injection following its over-RMB-100-million financing last August.

Photo provided by the interviewee

Dr. Wei Dong stated that Boya JiYin’s current main development directions are as follows:

1. Somatic gene editing therapy for β-thalassemia. This therapy involves extracting the patient’s autologous hematopoietic stem cells, genetically modifying them to restore relatively normal hematopoietic function, and then reinfusing them into the patient to achieve therapeutic objectives.

2. Universal CAR-T. This technology is a cellular immunotherapy that utilizes ex vivo genome editing techniques to engineer CAR-T cells. By employing gene editing to eliminate molecules on T cells that can trigger graft-versus-host disease (GVHD) and host-versus-graft reactions, this therapy enables the use of allogeneic CAR-T cells, thereby removing the limitation of relying solely on autologous cells. Compared with traditional CAR-T therapies, the manufacturing of universal CAR-T products via gene editing allows for more abundant and controllable sources of raw T cells, facilitating scalable, standardized, and commercialized production, which significantly reduces costs.

3. In vivo gene editing therapy. This therapy employs a proprietary technology developed independently of existing gene editing platforms, thereby circumventing the challenges associated with the in vivo application of technologies such as CRISPR. In the future, it will primarily target diseases affecting the liver, muscles, and nervous system.

4. High-throughput genomic screening services for drug development. Boya JiYin’s proprietary high-throughput CRISPR genome editing screening technologies enable functional analysis at the whole-genome level, paving new avenues for innovative drug research.

Among them, Boya Jiyin’s most cutting-edge project is ET-01, a blood therapy product for β-thalassemia.

When asked why the company chose beta-thalassemia treatment as its entry point, Dr. Wei Dong stated, “Currently, there are over 300,000 patients with intermediate and severe thalassemia in China, and the vast majority of those with severe disease do not survive beyond the age of 20. Traditional therapies for thalassemia mainly include regular blood transfusions combined with iron chelation, and allogeneic hematopoietic stem cell transplantation. The former requires long-term transfusions and the use of iron-chelating agents, which is costly and does not offer a cure. The latter is often limited by the difficulty of finding matched donors, with more than 80%–90% of patients unable to find suitable HLA-matched donors. Therefore, gene-editing therapy, which modifies a patient’s own cells to treat their disease, has the potential to become a new breakthrough in curing this condition.”

2018 was a particularly significant year for Boya Ji Yin. After years of research and development, the company’s hematopoietic cell platform for thalassemia and its universal CAR-T platform entered the preclinical development stage. During this period, Dr. Wei Dong returned to China and joined Boya Ji Yin as CEO.

Dr. Wei Dong holds a Ph.D. from Michigan State University, an MBA from the Wharton School, and a bachelor’s degree from Peking University. With over 20 years of experience in drug development and corporate management at multinational corporations, he has held clinical development or senior management positions at Deloitte Consulting, Johnson & Johnson Innovation, and Shire.

“Abroad, somatic gene-editing therapies for thalassemia have also entered clinical stages, but they are primarily targeted at the Caucasian population, and it remains unclear whether they are suitable for individuals of Asian descent. Therefore, when I learned that the development of gene-editing technology in China had finally reached the translational stage, was about to enter clinical trials, and had the potential to transform patients’ lives, I felt compelled to return and collaborate with my colleagues on this endeavor.”

Dr. Wei Dong stated that China’s gene-editing technology currently occupies a relatively forefront position internationally, lagging only one to two years behind the most advanced companies abroad.

“Like scientists, we look forward to more robust regulatory frameworks for research technologies that have a significant impact on humanity. However, with regard to gene editing, what I wish to convey to the outside world is that gene-editing technology is still in its early stages of development. Somatic cell gene-editing therapies and germline gene editing are like two sides of the same coin; they should be discussed separately under all circumstances,” said Dr. Wei Dong.