Retinitis Pigmentosa

Gene therapy shows particular promise for the treatment of ocular disease due to the accessibility, immune-privileged nature, and compartmentalization of the eye. Patients with retinitis pigmentosa (RP), a genetically heterogeneous disease that affects the photoreceptor cells of the retina, have benefited from gene therapy in recent decades. With the availability of profound gene therapy knowledge, certified technical staff, and numerous state-of-the-art instruments, Creative Biolabs has developed a series of gene therapy platforms in compliance with GMP regulations to manufacture and optimize both viral and no-viral vehicles for basic research and preclinical applications. Currently, adeno-associated virus (AAV)-based gene therapy for RP has been a hot research topic.

Brief Introduction of RP

RP initially presents as night blindness due to genetic deficits in the rod photoreceptors of the retina, finally leading to progressive visual loss. RP can be inherited as autosomal dominant (30-40% of cases), autosomal recessive (50-60%), or X-linked (5-15%). Currently, there are no treatments available for RP. The available treatments include the use of low vision aids, nutritional interventions, such as vitamin A palmitate and omega-3-rich fish, which are shown to slow the progression of RP patients. With the development of virology and immunology, gene therapy may be the next innovation for improving vision in young patients with RP.

AAV-based gene therapy for ocular disease. Figure 1. AAV-based gene therapy for ocular disease.

Current Status of RP Treatment by Gene Therapy

It is reported that RP progression is associated with more than 3000 mutations in over 200 genes. RP caused by mutations (modifications) in the genetic information can be corrected by in vivo gene delivery. Adeno-associated virus (AAV) has emerged as a favored vector for direct gene delivery due to its lack of pathogenicity and ability to incorporate into a variety of tissues in a directed manner. There were numerous cases have been reported about retinal gene therapy with AAV vectors.

  • Mutations in the RP2 gene account for a total of 10-20% of X-linked RP cases. Suddhasil Mookherjee, et al. designed and generated a self-complementary AAV8 vector containing human RP2 cDNA to treat X-linked RP. This AAV8-RP2 vector preserved cone function and promoted cone survival in an Rp2 knockout mouse model of RP.
  • Mutations in RP GTPase regulator (RPGR) account for over 70% of X-linked retinitis pigmentosa (RP) and 15% of all RP. Wu ZJ, et al. constructed AAV vectors carrying mouse or human RPGRorf15 full-length cDNA to prevent photoreceptor degeneration and preserve rod and cone function in the Rpgr-KO mouse retina. Importantly, the AAV8 human RPGRorf15 vectors fit the criteria for further clinical development.
  • Mutations in the CRB1 gene account for 70,000 persons with RP worldwide. Alves CH, et al. performed AAV-mediated CRB2 gene augmentation therapy for CRB1-RP to fight against blindness.
  • Deng WT, et al. had reported that mer receptor tyrosine kinase (MERTK)-associated form of autosomal recessive retinitis pigmentosa (arRP) can be remitted by AAV8 Y733F capsid mutant vector. This treatment realized long-term preservation of retinal function; it quickly restored MERTK expression before a significant debris field can incite apoptosis in photoreceptors.
  • Wang SK, et al. reported soluble CX3CL1 (sCX3CL1) may be a promising therapy to preserve cones and vision in patients with RP. They showed that AAV-mediated expression of sCX3CL1 prolonged cone survival in different RP models and improved visual function.
  • Usher syndrome (USH), a common combination of deafness and blindness due to RP, was usually caused by mutations in the large MYO7A gene. Dual AAV-MYO7A had gotten some positive clinical therapeutic effects.
  • AAV2/5-hPDE6B may cure the patients whose RP was caused by genetic defects in a gene called PDE6β, which caused retinal cells to progressively die as patients age, worsening their vision over time.

What We Can Do?

AAV-based gene therapy for RP has attracted increasing interests at Creative Biolabs. With high knowledge in the sensitivities and changing the landscape of gene therapy development, we employ principles of design excellence to provide gene therapy-related services that consistently meet customers' needs in every phase of development. Our gene delivery platform enables AAV design, AAV purification, AAV titration, AAV toxicity and safety determination to meet every specific demand. Proudly, all the AAV vectors we designed have been proven to infect and transduce a myriad of mammalian cell lines in vitro and a broad range of cell types in vivo. In addition, we can provide customized AAV services to address basic research and clinical applications. The large-scale AAV vectors we manufactured complyingly with all GLP, GMP, and GCP guidelines.

AAV services at Creative Biolabs. Figure 2. AAV services at Creative Biolabs.

AAV-based gene therapy researches are listed in development for different inheritance subtype of RP, positive data have demonstrated the therapeutic potential of AAV-based gene therapy in RP. Creative Biolabs has built a veteran team of scientists who have extensive hands-on experience supporting gene therapy development efforts for RP. We will also apply rich knowledge to lead bioanalytical testing of your promising gene therapy products.

Please feel free to contact us for more information.

For research use only. Not intended for any clinical use.