BendGen Therapeutics Advances Gene Delivery Platforms with Ophthalmology and Hematologic Disease Pipelines

In the early 21st century, as a frontier representative of the biotechnology field, gene therapy was still in its initial exploratory stage. “At that time, gene therapy did not appear as promising as we perceive it today. Due to various adverse reactions caused by gene therapy in patients (such as leukemia), the field hit rock bottom, with people seeing only the ‘high risk’ and ‘low druggability’ of gene therapy,” remarked Cai Yujia, founder of Bendao Gene, while reflecting on the history of gene therapy.

At that time, Cai Yujia was studying under Professor Thomas Perlmann (currently the Secretary-General of the Nobel Committee) at the Karolinska Institutet in Sweden. Immersed in a stimulating academic environment, he took Professor Perlmann—known for his humility and rigorous pursuit of truth—as his role model, motivating himself to adhere to his mentor’s highest academic standards.

Regarding gene therapy, which many viewed skeptically, Cai Yujia believes that “gene therapy is a precision treatment capable of curing diseases at their root; although it is imperfect at present, it represents the future.” Guided by this conviction, Cai completed his doctoral studies at the Karolinska Institute in Sweden and then moved to Aarhus University in Denmark, where he began his research on gene therapy under the supervision of Professor Jacob G. Mikkelsen.

Over the past decade of his scientific career, Cai Yujia has been dedicated to improving and developing gene therapies and their vector technologies. He explained to VCBeat the root causes of adverse reactions in gene therapy: “Gene therapy offers a perfect solution for curing rare diseases, but the delivery methods for gene drugs are not flawless. These imperfect drug delivery technologies are the fundamental cause of adverse reactions in gene therapy, which is precisely the problem I have been striving to solve over the past ten years.”

Cai Yujia, Founder of Bendao Gene

In 2018, after completing his doctoral studies, Cai Yujia founded Shanghai Bendao Gene Technology Co., Ltd. (hereinafter referred to as “Bendao Gene”), which was established in Minhang District, Shanghai. The company was co-founded by frontline gene therapy researchers from Shanghai Jiao Tong University, together with experts in pharmaceutical toxicology and industry professionals. Cai Yujia serves as CEO and Chief Scientist.

One reason for adverse reactions to gene therapy is the uncontrollable integration of viral vectors. One of Bendao Gene’s strategies to address this issue is the precise repair and modification of target genes. However, even with such targeted and precise gene editing, gene therapies still face the challenge of “delivery.” This leads to Bendao Gene’s second strategy: optimizing gene drug delivery technologies to ensure that gene therapies are safely and efficiently delivered to their target sites.

Bendao Gene has achieved safe and efficient delivery of gene-editing tools such as CRISPR through its leading virus-like particle (VLP)-based BDmRNA delivery technology, which ensures transient in vivo expression of gene-editing enzymes (Degradation within 72 hours), reducing the probability of off-target effects in gene editing and enhancing the safety of gene-editing therapeutics. The related research paper has been accepted by a high-impact Nature subsidiary journal.

Currently, the BD mRNA delivery technology has been granted a national patent and has entered the PCT phase.

Leveraging this technology platform, the company has independently established multiple clinical pipelines in gene editing, vaccines, and immunotherapy. For instance, with the BD111 pipeline for gene-editing therapy targeting herpes simplex keratitis (HSK), the company has demonstrated the efficacy and safety of the technology, ensuring that patients achieve an optimal benefit-risk ratio. Ethical approval has already been obtained from renowned Grade A tertiary hospitals.

Herpes simplex keratitis (HSK) is an infectious corneal disease caused by herpes simplex virus type 1 (HSV-1) and ranks among the most prevalent ophthalmic conditions worldwide. According to 2010 statistics, of the 8.248 million blind individuals in China, 4 million suffered from blindness due to corneal diseases. Infectious corneal diseases account for 85% of corneal blindness cases, with approximately 100,000 new cases reported annually. Currently, nucleoside analog drugs used to treat HSK can only inhibit viral replication and are unable to achieve complete eradication of the virus at its source.

By combining gene editing with its proprietary BDmRNA delivery technology, Bendao Gene has made it possible to safely and effectively cure herpes simplex keratitis (HSK). In the future, this technology is expected to replace corneal transplantation, thereby addressing the mismatch between the substantial market demand for donor corneas and their scarcity.

Furthermore, leveraging its BDmRNA technology, Bendao Gene has also established a pipeline targeting ophthalmic diseases such as wet age-related macular degeneration. Following the outbreak of COVID-19 in 2020, the Shanghai Jiao Tong University team led by Dr. Cai Yujia utilized its core BDmRNA delivery technology to develop a BDmRNA candidate vaccine against coronaviruses. The team released the world’s first animal data for an mRNA vaccine, garnering widespread attention from media outlets and academic institutions both domestically and internationally.

In addition to the delivery technology for transient expression of BDmRNA, Bendao Gene has also developed a corresponding delivery platform, “BDlenti,” for gene therapies requiring long-term in vivo expression. This platform is primarily designed for gene medicines that require lentiviral vector delivery, such as gene therapies targeting indications in the hematopoietic system and ophthalmic diseases.

Cai Yujia revealed that, compared with conventional lentiviral vector delivery, the BDlenti delivery technology incorporates unique optimization strategies to reduce the risk of insertional mutagenesis, while enabling long-term expression of therapeutic genes in patients without loss of efficacy due to gene silencing.

Leveraging its BDLenti delivery technology, Bendao Gene has also developed several clinical pipelines targeting the hematopoietic system. Among these, BD211, a gene therapy candidate for thalassemia, represents an internationally advanced and domestically leading therapeutic option, offering more advanced, comprehensive, and curative treatment for pediatric patients with severe thalassemia. One of the key uses of the funds raised in Bendao Gene’s pre-A financing round, completed in June, is to accelerate the entry of the BD211 pipeline into clinical trials. The company’s hematopoietic gene therapy projects will be conducted in collaboration with top-tier hospitals, including Ruijin Hospital affiliated with Shanghai Jiao Tong University.

Currently, Bendao Gene has established a comprehensive lentiviral vector design and manufacturing platform, which can significantly enhance the quality and yield of viral vectors. The BDmRNA technology is built upon Bendao Gene’s manufacturing platform, holding promise for the development of globally leading, China-made innovative gene therapy drugs. Furthermore, the company has developed a domestically leading hematopoietic stem cell manufacturing process, which can improve the delivery efficiency of gene therapies and reduce the cost of gene treatment.

The company has established a complete core team covering project R&D, preclinical studies, CMC, and regulatory submission. A standard new drug process development center of nearly 1,000 square meters is also about to be completed.

Recently, Bendao Gene has also initiated a new round of Series A financing, with the proceeds primarily allocated to advancing the BD111 and BD211 pipelines to complete their Investigational New Drug (IND) applications.