JCI: new technology improves the effect of gene therapy on vision

October 1, 2019 / BIOON / -- in experiments based on rats, pigs and monkeys, researchers at Johns Hopkins University School of medicine developed a gene therapy to save vision If it is proved to be safe and effective for human beings, the technology can provide a new and more durable treatment option for patients with common diseases such as wet age-related macular degeneration (AMD), and it may replace the defective genes in patients with hereditary retinopathy This new method was published in the Journal of clinical investigation recently The method uses a small needle to inject harmless, genetically engineered virus particles into the space between the whites of the eyes and the vascular layer of the eyes (known as the suprachoroidal cavity) From there, the virus can transfer the therapeutic gene to retinal cells (image source: www Pixabay Com) although currently only tested in animals, the new suprachoroidal injection technology is less invasive, because it does not involve the separation of retina, and can be carried out in the outpatient clinic in theory, which marks the emergence of a new gene therapy for vision According to the National Institute of Ophthalmology, macular degeneration is the main cause of irreversible and disabling vision loss in people over 50 years old An estimated 10 million Americans suffer from the disease Abnormal blood vessels grow under the retina and penetrate the fluid with poor vision into the eyes The abnormal growth and leakage of blood vessels are caused by excessive production of cell signals called vascular endothelial growth factor (VEGF) At present, ophthalmologists can prevent vision loss by injecting VEGF blocking proteins into the eyes, but the maintenance time of these treatments is limited, so patients must return to the clinic every four to six weeks to have more injections to maintain vision Missing treatment may lead to abnormal vascular growth, which may lead to vision loss "We found that although repeat therapy is effective, it is difficult for patients to keep up with it As time goes on, they will gradually lose their vision," campochiaro said However, gene therapy can permanently produce anti VEGF protein in every cell in the retina, so as to maintain vision without repeated injection In order to test whether the suprachoroidal injection technology can effectively provide gene therapy to the retina, researchers first want to track whether the technology can make the virus reach the back of the eye The researchers injected the eyes of 10 rats with innocuous forms of adeno-associated viruses modified to carry fluorescent markers into the suprachoroidal space of the eyes They used a high-power microscope to track the virus and found that it had reached the entire retina a week later Next, the researchers looked at whether the virus could provide useful genes They loaded the anti VEGF gene into their modified virus and injected it into the suprachoroidal space of 40 rats that were induced to develop human macular degeneration For comparison, they gave regular subretinal injections in 40 other rats The researchers found that the suprachoroidal injection technique was as effective and durable as the traditional subretinal method in delivering the anti VEGF protein for vision protection By conducting these experiments in pigs and rhesus monkeys, the researchers confirmed that the suprachoroidal delivery method is suitable for larger animals, whose eyes are closer to human eyes All the results are similar Although the gene therapy is promising, campochiaro points out that it may not be a good option for people who have previously had similar experiments because their immune system may block the virus Research advance search for safer, easier way to deliver vision saving gene therapy original sources: Kun Ding, Jikui Shen, zibran Hafiz, Sean F Hackett, Raquel Lima e Silva, Mahmood Khan, Valeria E lorenc, daiqin Chen, Rishi Chadha, mini Zhang, Sherri van everen, Nicholas bus, Michele fiscella, Olivier danos, Peter A Campochiaro AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression Journal of Clinical Investigation , 2019; DOI: 10.1172/JCI129085