Achromatopsia
Achromatic color ablation (achromatopsia) belongs to complete cone dysfunction, which is exactly the opposite of night blindness (rod cell dysfunction). Patients are especially dark, photophobic, and manifested as blindness seriously, with only the distinction between light and dark, and no color difference. Moreover, there are symptoms such as poor vision, amblyopia, central dark spots, and oscillating nystagmus for achromatopsia patients. It is the most serious type of color vision disorder and is less common in patients. Pathogenic genes are mainly CNGA3, CNGB3, GNAT2, PDE6H, PDE6C and ATF6. Adeno-associated virus (AAV) vectors in gene CNGA3 delivery therapy for achromatopsia have entered phase I clinical trials. Based on the latest research progress, Creative Biolabs provides comprehensive gene therapy technologies and services to improve the symptoms of achromatopsia.
Figure 1. Summary of the genes known to cause achromatopsia. (Hassall, 2017)
AAV Vectors for Clinical Therapy of Achromatopsia
Currently, scientists have designed AAV vectors by carrying cone-specific promoter fragments to offset the congenital cone photoreceptor dysfunction. So far, similar studies have been registered for four applications. Encouragingly, three of them are already in clinical trials. Besides, scientists have used AAV vectors in eight animal models to genetically treat the disease in preclinical research.
- AAV Vectors Restore Retinal Function in the Sheep Model
Achromatopsia is mainly caused by mutations in the CNGA3 gene. According to reports, inserting a complete CNGA3 gene from humans into the AAV vector, following successfully delivered into the sheep subretinal can get a long-term recovery of visual function. The sheep in the drug-administered group used a short time to pass through the maze and rarely collided, compared with the control group. More importantly, so far, the efficacy has been maintained for three years, with no side effects.
- AAV Vectors Improve Vision in the Mouse Model
The pathogenic genes are GNAT1, OPN4 and CNGA3 in the mouse model for achromatopsia. Researchers have demonstrated that the transplant of AAV vectors to increase CNGA3 gene expression can effectively increase the function of the retina. Electroretinogram (ERG) and optomotor response (OMR) are clinically used to evaluate retinal function. After AAV vector is injected into the mouse retina, ERG rescue was about 40 to 50 percent. Moreover, ERG rescue was up to 80% after three weeks of continuous administration, which means that gene therapy using AAV vectors can improve the condition of achromatopsia in the mouse model.
Figure 2. Gene replacement therapy for retinal degeneration. (Scholl, 2016)
AAV vectors are widely used in the treatment of ophthalmic diseases due to its non-toxic advantages. Creative Biolabs provides a full range of vector design and gene delivery services, especially in eye diseases, for example, achromatopsia. Please contact us in time for more information and we are happy to offer the best service and guidance for you.
References
- Hassall, M.M.; et al. (2017). Focus: Genome Editing: Gene Therapy for Color Blindness. Yale J Biol Med. 90(4): 543-551.
- Scholl, H.P.N.; et al. (2016). Emerging therapies for inherited retinal degeneration. Science Translational Medicine. 8(6): 368-379.
