Tetrahedral Framework Nucleic Acid Technology in Ophthalmic Disease Treatment

The globally pioneering tetrahedral framework nucleic acid drug delivery system has successfully completed mechanism studies, cellular pharmacology validation, and non-clinical animal model validation in addressing the challenges of retinal neovascular diseases, achieving groundbreaking results. This delivery system was developed by Professor Yunfeng Lin’s team, the first award winner from mainland China at the IADR, and industrialized by Professor Delun Luo’s team at Yunhai Biotechnology.

Over 20 years ago, when Professor Yunfeng Lin, one of the founders of Yunhai Biotechnology, was a newly emerging medical researcher, he was introduced to framework nucleic acids by Academician Chunhai Fan. This marked the beginning of his deep involvement in developing novel drug delivery systems and nucleic acid drug research. In 2015, Professor Yunfeng Lin met Professor Delun Luo, the project leader of the highly prestigious ophthalmic bioproduct “Conbercept” in China. After intense discussions, framework nucleic acids, initially met with skepticism and verification, were rediscovered and led to the creation of “Yunhai Biotechnology,” akin to the “base pair complementarity” in genetics. This endeavor epitomizes the goal of “benefiting more patients” and reflects the essence of perseverance in medical research. Recently, Yunhai Biotechnology has shared its groundbreaking research findings on major blinding eye diseases, such as retinal neovascularization.

Retinal neovascularization is a major cause of irreversible vision impairment and blindness for millions of patients worldwide. It includes several blinding retinal diseases such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). Current treatments include anti-vascular endothelial growth factor (VEGF) drugs and retinal laser photocoagulation, but both have significant drawbacks. For example, inhibiting VEGF signaling may affect the growth of normal retinal blood vessels, and laser treatment can cause retinal tissue damage and complications. Furthermore, ischemia and hypoxia can further cause irreversible damage to retinal nerve cells. To date, there is still a lack of safe and effective methods for neuroprotection. Therefore, there is an urgent need to optimize treatment strategies for retinal neovascularization.

“If we compare the eye to a camera, the current major causes of blindness that are difficult to address in global ophthalmology have shifted from traditional 'optical path diseases'—which affect light transmission and zoom projection—to 'visual pathway diseases'—which impact imaging and transmission. The first station of the 'visual pathway' is the retina. The human retina is the most intricate photoreceptive and visual processing system, composed of hundreds of millions of photoreceptor cells and connected to the brain via the optic nerve. Due to the rich vascular network and numerous non-regenerable nerve cells in the retina, any damage can directly lead to visual impairment or even complete loss of vision. Diseases causing retinal damage, such as age-related macular degeneration, hereditary retinal degeneration, and diabetic retinopathy, have become major causes of blindness in humans.”

Professor Xiaoyan Ding, who served as the clinical director at the Zhongshan Ophthalmic Center for many years, has deeply felt the frustration of having no medication available for patients. In the retina disease clinic, whenever a patient asks her, “Doctor, will I go blind?” she can only offer comfort by saying, “No, medical technology is continually advancing, and there will definitely be opportunities.”

Global innovations in ophthalmic diagnostic and therapeutic devices and drugs are continually emerging, including new technologies and drugs such as vitrectomy equipment, cataract phacoemulsification devices, various laser diagnostic and therapeutic tools, prostaglandin-based anti-glaucoma drugs, and anti-VEGF drugs. More importantly, China has nearly synchronized each technological breakthrough, providing thousands of patients with the chance to regain their sight and inspiring Chinese ophthalmology research to delve deeper.

In the face of research and industrial development, all preparations are never enough; the only thing one can prepare for is “persistence.”

In the retinal RIR rat model, the experimental drug significantly increased the number of retinal ganglion cells (RGCs) across three dose groups, with statistically significant differences. This suggests effective treatment of RGC loss due to ischemia-reperfusion and demonstrates a favorable dose-response relationship.

Figure 1: Retinal Ganglion Cell Count

From left to right: Normal Group, Negative Control Group, Low Concentration Experimental Drug Group, Medium Concentration Experimental Drug Group, High Concentration Experimental Drug Group.

In fact, the retinal OIR mouse model shows that the experimental drug not only inhibits the area of pathological neovascularization (Figure 2) but also promotes physiological vascular development in areas of vascular occlusion (Figure 3). Therefore, the experimental drug not only alleviates abnormal blood vessel growth but also aids in the restoration of the normal vascular system in ischemic retinas by reducing vascular occlusion. This study highlights the innovative potential of the experimental drug as a treatment option for ischemic retinal diseases, which are a major cause of blindness in both developed and developing countries worldwide.

Figure 2: Retinal neovascularization area

Figure 3: Retinal vascular occlusion area

From left to right: Normal Group, Negative Control Group, Positive Control Group, Drug 1 Group, Drug 2 Group, Experimental Drug Group.

At Yunhai Biotechnology, every individual engaged in medical research and industrial development harbors a deep-seated ideal, and it is this ideal that inspires them to persist through the challenges of entrepreneurship. Every step of Yunhai Biotechnology's growth is achieved with the support of various upstream and downstream resources and the collective efforts of many people. The company looks forward to the next breakthrough of the tetrahedral framework nucleic acid (tFNA) delivery system in addressing clinical challenges related to retinal diseases.