Yang Hui, an 85s Scientist-Entrepreneur, Aims to Become a Model of Industry-Academia Integration with Huidagene

After finishing his work in the laboratory, Yang Hui left the Chinese Academy of Sciences’ Institute of Neuroscience, located at 320 Yueyang Road in the heart of Xujiahui, Shanghai, and hurriedly made his way to Free Trade Zone No. 1 Life Science and Technology Industrial Park at 215 Fute South Road, in the northeastern corner of Shanghai.

Yang Hui’s startup, Hui-Gene (short for Hui-Gene Therapeutics), is located within the Free Trade Zone No. 1 Industrial Park, occupying two buildings with a total area of approximately 10,000 square meters. Over the past three to four years, he has frequently commuted between the Institute of Neuroscience and Hui-Gene. On one hand, he supervises doctoral students and postdoctoral researchers in their scientific work at the institute’s laboratory; on the other, he closely monitors the research and development progress at Hui-Gene.

This August, Yang Hui shifted his professional focus from the laboratory to Hui-Gene Therapeutics, marking a turning point in his career.

Our first meeting took place in the sixth-floor offices of Hui-Gene Therapeutics at the Free Trade Zone No. 1 Industrial Park. Yang Hui was wearing a simple white T-shirt, looking no different from the doctoral students who hurried through the laboratory corridors carrying petri dishes and notebooks. Four years into his entrepreneurial journey, Yang Hui still carries the reserved demeanor characteristic of scientists.

When Hui-Gene Therapeutics was first established, Yang Hui encountered the challenges commonly faced by scientists turning entrepreneurs. “I had great confidence in my scientific and technical expertise, but lacked experience in industrial-scale production. The development Hui-Gene has achieved today is the result of our persistent trial-and-error exploration along the way.”

When Yang Hui first started his venture, the team had to deal with a myriad of tedious matters, ranging from corporate operations to the renovation of laboratories and offices. Fortunately, these responsibilities were entrusted to Yao Xuan, a fellow Ph.D. student who co-founded the company and currently serves as CEO of Hui-Gene Therapeutics. This arrangement allowed Yang Hui to focus exclusively on scientific research and technological development during the early stages of Hui-Gene Therapeutics.

Currently, within Hui-Gene Therapeutics’ R&D team of approximately 100 members, two to three dozen are former students of Yang Hui, just like Yao Xuan.This year, Hui-Gene Therapeutics established an Innovation Research Institute and reorganized its core R&D teams within the company. The institute comprises seven research groups: DNA Tools Group, RNA Tools Group, AAV Delivery Group, LNP Delivery Group, Vision and Hearing Group, Muscle Metabolism Group, and Neurological Diseases Group, covering the entire early-stage gene therapy drug development pipeline. Hui-Gene’s R&D laboratories feature nearly 7,000 square meters of experimental space.

Unlike in research institute laboratories, as the company’s R&D team continues to expand, there is a growing need for more precise control over R&D directions, along with increasing time pressures.Previously, a laboratory would focus on only one specific area; now, Hui-Gene Therapeutics' R&D team is equivalent to a small research institute,From the discovery and evolution of gene-editing tools to their application, every aspect must be addressed. He is responsible for making decisions on the advancement of key pipelines, and he also needs to devote more time and energy to corporate operations.

For Yang Hui, Hui-Gene Therapeutics has released multiple research achievements in the four years since its establishment. By the end of this year, Hui-Gene Therapeutics plans to submit Investigational New Drug (IND) applications in both China and the United States for a gene replacement therapy pipeline. This signals that Hui-Gene is gradually reaching maturity in the research and development, manufacturing, regulatory registration, and clinical stages of gene therapies. Meanwhile, the company has completed a Series C financing round amounting to hundreds of millions of yuan, marking a new phase in its corporate development.

From the outset of his entrepreneurial journey, Yang Hui benchmarked against leading companies in the overseas gene therapy sector, such as Alnylam, which spent seven years laying its foundation. Yang began developing his technological toolkit in 2016, and this year marks the seventh anniversary, with various tools now largely ready for deployment.

Coming from research institutes to drive commercialization in the industry, and benchmarking against leading global companies from the outset of his entrepreneurial journey, Yang Hui’s philosophy largely represents the post-1985 “new generation of scientist-entrepreneurs.”：They are strengthening basic research and emphasizing originality, while placing greater importance on competing on the same stage as global enterprises.

In May last year, Yang Hui’s team discovered two new classes of CRISPR/Cas13 systems through computational analysis of large-scale microbial metagenomic data. By conducting functional experiments and engineering modifications, they developed a set of highly efficient and specific RNA editing tools, Cas13X and Cas13Y2. In January this year, the foundational patents for Cas13X/Y were officially granted by the U.S. Patent and Trademark Office, making them the first independently developed CRISPR-Cas13 gene-editing tools in China with freedom to operate.

On August 11 this year, Hui-Gene Therapeutics and the team led by Yang Hui from the Center for Excellence in Brain Science and Intelligence Technology (Institute of Neuroscience), Chinese Academy of Sciences, published a new research paper titled “High-fidelity Cas13 variants for targeted RNA degradation with minimal collateral effects” in the journal Nature Biotechnology. Through a series of screenings, the study identified high-fidelity Cas13 mutants (hfCas13d and hfCas13X) that exhibit efficient degradation of target RNA while significantly reducing collateral cleavage activity, thereby opening new avenues for the safe application of the CRISPR-Cas13 system.

The continuous optimization of tool efficiency and safety, identification of the most suitable indications, and advancement of subsequent clinical trials are the current R&D focus of Yang Hui’s team.

“Previous DNA editing tools were dominated by Cas9, but China does not hold the core patents for Cas9. To my knowledge, no company in China has currently obtained a patent license for Cas9 to be used in the development of innovative drugs.”These issues will inevitably become urgent problems that some Chinese pharmaceutical companies need to address.“We now have our own underlying technology platform, Cas13X/Y, which enables us to continuously optimize tools and develop pipelines on this platform.”

Prior to this, patents related to CRISPR-Cas technology were predominantly held by European and American companies. It is reported that Hui-Gene Therapeutics’ CRISPR-Cas13X/Y has broken the patent monopoly held by Western countries in the field of gene-editing tools, thereby resolving patent restrictions for the future development and commercialization of gene-editing technology products in China. “I hope that all tools developed by Hui-Gene will be fully accessible through licensing channels to agricultural companies, cell therapy companies, and nucleic acid testing companies worldwide.” Yang Hui believes that this reflects the responsibility expected of him and his team as scientists, and of Hui-Gene as a Chinese enterprise.

It is reported that Hui-Gene Therapeutics will soon launch its independently developed DNA editing tool, Cas12Max, and its DNA single-base editing tool, Base Editor 2.0. Both products hold independent intellectual property rights and offer significant advantages in terms of efficiency, delivery, and specificity.

The newly established Innovation Research Institute this year aims to develop robust foundational gene-editing and delivery tools, and to conduct proof-of-concept studies for novel drug pipelines. According to reports, the institute’s goal is to continuously generate first-in-class and best-in-class, rather than fast-follow, drug candidates capable of advancing to the Investigational New Drug (IND) application stage.

Currently, three pipelines centered on Cas13X/Y have officially entered the clinical trial application stage. These three pipelines are not only first-in-class novel drugs but also represent the first global clinical trials for Cas13.“We have completed three this year, and our goal for the next five years is to have 15–20 Class I new drugs enter IND filing.”Yang Hui said.

During the years Yang Hui was studying, the domestic biomedical field generally held that basic research was an elite pursuit, while industrial translation was considered somewhat vulgar.

“In the past, those engaged in basic research in China were opposed to starting businesses."We were taught that scientific research must be highly focused, with little consideration given to commercialization. At that time, even those who founded companies did so discreetly.""Yang Hui has the most direct feelings about this."

In contrast, universities and research institutes abroad boast a vibrant entrepreneurial culture, where most postdoctoral researchers, after achieving certain results, seek to establish companies to translate their technologies into clinical applications for the benefit of patients. Moreover, the close ties between the academic and industrial sectors in the overseas biopharmaceutical field facilitate more direct and efficient resource interaction.

Kendall Square in Cambridge, Massachusetts, where Dr. Yang Hui pursued his postdoctoral research at the Massachusetts Institute of Technology (MIT), is also a globally renowned hub for intensive life sciences innovation. Many prominent scientists, including George Church and Feng Zhang, are based there. MIT is hailed as the most successful university in integrating industry, academia, and research. The Boston Globe once vividly described Kendall Square as “a beating heart, with MIT as its aorta.”

There is a comprehensive entrepreneurial ecosystem and a strong culture of innovation. Yang Hui observed that top-tier international journal publishers, such as Cell Press, are located right next to the university, while platform service providers like Addgene and The Jackson Laboratory are also in close proximity. Major biopharmaceutical companies are situated within a one-kilometer radius. “If we have a promising achievement to commercialize or seek collaboration on, we can approach them directly. Moreover, their headhunters and business school representatives actively visit various laboratories to understand our research.”

Resource integration has subtly reshaped the perceptions of overseas researchers, leading many to naturally embrace this approach.— When founding a company to facilitate the translation of scientific research, investors will provide a comprehensive suite of support services, including company registration, management, funding, patents, resources, talent acquisition, and industrial infrastructure, along with competitive compensation packages.

It can be said that the cultivation of a research-industry ecosystem and the entrepreneurial atmosphere in academia are mutually reinforcing. For China’s biopharmaceutical industry to achieve sustainable development and attain international leadership, both elements are indispensable.

Yang Hui believes that industrial translation is as meaningful as basic scientific research, with the only difference being their respective objectives. While the importance of fundamental theoretical research is undeniable, certain projects suitable for translation can also be advanced within the industry, potentially achieving faster implementation and greater societal benefit.

“In interviews, Yang Hui has repeatedly emphasized that China’s foundational R&D capabilities in CRISPR technology are on par with those of Europe and the United States, placing them on the same starting line; the primary weakness of China’s biopharmaceutical industry lies in translation and commercialization.”

“If I can set an example by demonstrating the significance and prospects of translating scientific research into industrial applications, I can gradually foster an atmosphere that attracts talent interested in commercialization to join the industry.“At least two to three dozen PhD students and postdoctoral fellows at Hui-Gene Therapeutics have already entered the industry sector under his subtle influence.”

This is undoubtedly a positive signal.The scientist-capital collaboration model adopted by Yang Hui represents a major trend in the overseas biopharmaceutical industry, yet it still requires sustained promotion within China.. A successful entrepreneur and a startup that excels in translating scientific research into commercial applications inherently possess a powerful magnetic field capable of reshaping the zeitgeist,Yang Hui hopes to become a success story.

In the explorations of Yang Hui and a new generation of entrepreneurs, industry-academia-research collaboration will also inject the vital energy of source innovation that the industry urgently needs.