YolTech Therapeutics Files for IPO: Pioneering In Vivo Gene Editing with LNP Delivery to Overcome AAV Limitations

We are in an era of booming development in biomedicine. While antibody drugs and small-molecule drugs have benefited numerous patients, a growing array of novel therapies has emerged, demonstrating robust therapeutic efficacy and promising prospects for future development. Among these, gene editing technology has garnered the most attention.

From the discovery of viral-resistant gene sequences in ancient bacteria to the birth of CRISPR technology, and from the Nobel Prize awarded for gene editing to the entry of CRISPR-based gene-editing therapies into clinical trials, gene-editing technology has overcome numerous obstacles to emerge as a rising star in the field of biomedicine.

Both domestically and internationally, a growing number of pharmaceutical companies have entered the field of gene editing technology, aiming to leverage this therapeutic approach as a breakthrough in disease treatment.If gene editing technology is a mighty wave in the surging tide of the biopharmaceutical era, then YolTech Therapeutics is the trailblazer in the field of gene editing, leading the development of gene editing technology in China.

YolTech Therapeutics is a biotechnology company focused on in vivo mRNA delivery technologies and gene editing technologies. By continuously developing and optimizing CRISPR-Cas, base editing, and other next-generation gene editing tools, as well as implementing innovative improvements to next-generation mRNA production platforms and lipid nanoparticle (LNP) assembly processes, the company develops in vivo gene editing therapeutics for genetic diseases and cardiovascular diseases.

Dr. Wu Yuxuan, founder of YolTech Therapeutics, joined the Shanghai Institute of Biochemistry and Cell Biology at the Chinese Academy of Sciences as a postdoctoral fellow and associate researcher after earning his Ph.D. from Wuhan University in 2013. There, he began researching CRISPR/Cas9-mediated gene editing technologies to explore novel therapeutic approaches for genetic disorders. Recognizing the future potential of gene editing, particularly in hematopoietic stem cells (HSCs), Dr. Wu chose to further his work at Harvard Medical School and Boston Children’s Hospital. Conducting research in one of the world’s leading HSC laboratories, he focused on combining CRISPR gene editing with HSC studies. During this period, he developed a CRISPR-based gene therapy technique for HSCs that treats thalassemia and sickle cell disease by efficiently activating fetal hemoglobin expression.

After returning to China in 2018, Dr. Wu Yuxuan joined East China Normal University as a researcher and concurrently served as a co-founder of Biocytogen (Bangyao Bio), dedicating himself to advancing gene-editing technologies toward clinical application. In 2020, Dr. Wu’s research team achieved a major breakthrough: in collaboration with Xiangya Hospital of Central South University, they successfully treated two patients with severe β0/β0 thalassemia using CRISPR gene editing. This marked not only the first case in Asia of treating thalassemia with gene-editing technology but also the first successful case worldwide of treating severe β0/β0 thalassemia using CRISPR gene editing.

Dr. Wu Yuxuan’s extensive academic and professional experience has laid a solid theoretical foundation for YolTech Therapeutics’ development in the field of gene editing.

Currently, gene editing therapies are categorized into two types: ex vivo gene editing and in vivo gene editing. Ex vivo gene editing involves collecting cells from patients, editing them, and then reinfusing the modified cells back into the patient as a therapeutic agent. In contrast, in vivo gene editing refers to the direct delivery of gene editing systems to the diseased site within the patient via vectors for disease treatment.

Nowadays, ex vivo gene editing therapies are advancing more rapidly than in vivo gene editing. The scientists hailed as the “CRISPR Big Three” have all founded gene editing companies, with each having ex vivo gene editing therapies enter clinical stages. However, after years of research and exploration into gene editing technologies, Dr. Wu Yuxuan believes that in vivo gene editing holds greater development prospects in the future due to its broader range of application scenarios. First,In the view of Dr. Wu Yuxuan,Gene editing technology is trending from ex vivo editing toward in vivo editing.“I believe that in vivo gene editing will not only have the potential to replace therapies such as cell therapy in the future, but may even be capable of performing tasks traditionally handled by conventional gene therapies. For instance, indications currently treatable using AAV vectors could also be addressed by in vivo gene editing in the future.”

Secondly, Dr. Wu Yuxuan stated, “Given China’s national conditions, it is impossible for our drug costs to be priced at one or two million US dollars, as is often the case in the United States. Such treatment costs are difficult for domestic patients to bear.” In his view, gene-editing technologies based on cell therapy face significant hurdles in process scale-up stability and production capacity due to their personalized customization characteristics. Additionally,The prohibitive cost of ex vivo gene editing therapies will limit their application to a broader patient population.

Drawing on his profound insights into the field of gene editing, Dr. Wu Yuxuan has positioned in vivo gene editing as the strategic entry point for YolTech Therapeutics.

Currently, both gene editing technology and in vivo mRNA delivery technology are in a growth phase. However, YolTech Therapeutics has clearly defined its development path, aiming to achieve breakthroughs in gene editing therapy by combining LNP delivery systems with in vivo gene editing.

In the Era of In Vivo Gene Editing,YolTech Therapeutics has established its technological advantages by focusing on three core areas: gene-editing tools, LNP-based drug delivery systems, and manufacturing processes.

YolTech Therapeutics is dedicated to the discovery of innovative gene-editing tools,YolTech Therapeutics has made innovative strategic deployments in traditional CRISPR-Cas-based gene editing tools, as well as next-generation gene editing technologies such as base editing and prime editing.“Our goal is to develop innovative gene editors with independent intellectual property rights, so as to strengthen the company’s future international expansion, drive the development of China’s gene editing industry, and help domestic peers break free from patent blockades on gene editing tools.”

In addition to gene editors, YolTech Therapeutics has also accelerated its R&D efforts in mRNA delivery systems. The company focuses on non-viral vectors, represented by lipid nanoparticles (LNPs). The mRNA encoding gene editors must be delivered into the body via LNP carriers to edit target genes and exert therapeutic effects. YolTech Therapeutics aims to combine in vivo gene editing with LNP delivery systems to accelerate the promotion and application of gene editing technologies.

Dr. Wu Yuxuan stated, “In terms of industrial-scale manufacturing, LNP delivery systems are more akin to traditional small-molecule or large-molecule drugs. Leveraging their production advantages, it is possible to manufacture drug batches for a large number of patients, store them after quality control, and subsequently administer them to each patient, thereby significantly reducing costs. In my view, therapeutic approaches that combine in vivo gene editing with LNP-mediated in vivo delivery represent the future of gene-editing treatment strategies.”

Regarding delivery systems, the most prominent candidates currently are viral vectors represented by adeno-associated virus (AAV) and non-viral vectors represented by lipid nanoparticles (LNPs). Dr. Wu Yuxuan believes that AAV vector-based therapies have certain limitations, whereas LNP delivery systems can circumvent these issues: “First, many patients already possess pre-existing antibodies against AAV, rendering AAV-based therapeutic strategies unsuitable for those individuals. Second, it was previously believed that AAV remains episomal and does not integrate into the host genome; however, recent studies have shown that AAV can integrate into the genome at a low frequency. This integration is random, and if it occurs in critical genomic regions, it may pose an oncogenic risk. Third, although current AAV vectors have achieved prolonged dosing intervals in diseases affecting the eye and liver, their inability to integrate into the genome means they are diluted as cells divide, necessitating repeated administration. Moreover, if immunogenicity develops after the initial AAV injection, subsequent treatments cannot be administered, making it difficult for AAV to achieve a lifelong cure for any given disease.”

YolTech Therapeutics is poised to break through the limitations of AAV therapy.

“By combining gene editing with LNP delivery systems, it is possible to site-specifically insert exogenous DNA fragments into designated locations within the genome, thereby avoiding random integration and enhancing the safety of gene therapies. Moreover, LNPs do not exhibit the immunogenicity associated with AAV vectors, thus eliminating concerns regarding patient ineligibility due to immune responses.“Furthermore, Dr. Wu Yuxuan also believes that ‘gene editing + mRNA + LNP delivery’ will provide an ideal combination approach for nucleic acid therapeutics. Currently,”The challenges of mRNA drugs lie in their rapid degradation and the need for repeated administration, while also requiring a high expression threshold to exert therapeutic effects. If combined with in vivo gene editing, it may be possible to transform repeated dosing into a one-time treatment that offers lifelong cure.

Building on its technological innovations, YolTech Therapeutics has also made significant efforts and attempts in process scale-up. Dr. Wu Yuxuan stated, “Achieving in vivo gene editing at the laboratory scale with favorable therapeutic outcomes is merely a small step; there is still a long way to go before a true drug product can be developed. To develop a marketable drug, process scale-up is essential to ensure large-scale, single-batch manufacturing. Meanwhile, this scale-up must maintain the therapeutic efficacy of in vivo gene editing, thereby ensuring strong druggability.”YolTech Therapeutics has established a uniquely advantageous process scale-up system and a series of quality control systems through long-term exploration, which will become our core strategic focus in the future.”

Currently,YolTech Therapeutics has attracted outstanding talent from diverse fields, including scholars from top domestic and international academic institutions such as Harvard University, East China Normal University, and the Chinese Academy of Sciences, who lead innovative R&D efforts, as well as core experts from renowned U.S. mRNA and gene-editing pharmaceutical companies, who oversee process optimization and scale-up for manufacturing.

With the support of this exceptional founding team, YolTech Therapeutics has achieved in vivo validation across multiple animal models within just six months of its establishment.In mouse liver tissues, the editing efficiency exceeded 80%, approaching the upper limit for this tissue type; in non-human primate (NHP) studies, the liver editing efficiency reached levels comparable to those of leading global companies, with a single injection achieving 60–70% knockdown of the target protein.Moreover,YolTech Therapeutics has leveraged its proprietary gene-editing tool discovery platform to identify novel editing tools eligible for international patents, positioning the company to potentially become the first in China to advance an in vivo gene-editing pipeline into clinical trials.

Leveraging the synergistic advantages of in vivo gene editing and lipid nanoparticle (LNP) delivery systems, YolTech Therapeutics has gradually clarified its future development strategy. The company will conduct more in-depth exploration and research and development in core technologies: in terms of gene editing, YolTech will continuously screen and discover next-generation gene editing tools that are highly efficient and safe to comprehensively meet diverse editing needs; regarding delivery methods, YolTech plans to persistently develop various lipid materials with independent intellectual property rights, thereby enriching its portfolio of delivery vectors targeting the liver and other tissues and organs.

In terms of its product pipeline, YolTech Therapeutics has established R&D layouts in the fields of genetic diseases and cardiovascular diseases, aiming to advance its products to the clinical trial application stage as soon as possible, while further optimizing and upgrading its liver-targeted LNP delivery system. Regarding long-term planning, YolTech Therapeutics will also attempt to develop delivery systems for other tissues and organs at the basic research level, so as to extend the application of gene editing technology to a broader range of disease treatments.

In terms of team building, YolTech Therapeutics plans to recruit more professionals with medical backgrounds to advance product clinical registration and future clinical trials. Meanwhile, the company will also bring in strategically minded talent from the industry to further optimize drug manufacturing processes and develop an innovative drug pipeline, foster strategic collaborations with major pharmaceutical companies both domestically and internationally, and make ample preparations for global expansion.

When asked why he named the company YolTech Therapeutics, Dr. Wu Yuxuan’s response reflected his deep commitment to the field of biopharmaceuticals and his high hopes for the company’s future: “As a Chinese innovative pharmaceutical enterprise, I wanted our name to embody China. I believe that Yao and Shun, two legendary sage-kings, symbolize the Chinese cultural aspiration for governance through virtue and meritocracy. Beyond scientific innovation, corporate governance and humanistic care are paramount; the cultural values represented by Yao and Shun remain highly commendable in today’s era. Furthermore, as we all know, the Tang Dynasty was a golden age characterized by exceptional inclusivity and diversity, representing the pinnacle of Chinese culture. I hope that YolTech will, like the Tang Dynasty, expand globally with representative biopharmaceutical products. Meanwhile, the Tang Dynasty also exemplified cultural inclusiveness. In the future, YolTech will embrace an international perspective and attract top global talent with an inclusive mindset, jointly creating a great era in biopharmaceuticals.”

In the future, YolTech Therapeutics will build on its foundation in in vivo gene editing to continuously expand and explore new indications, develop more innovative therapies, provide novel solutions for unmet medical needs, and offer superior treatment options to patients worldwide.