Gene therapy for inherited retinal diseases: progress and possibilities
| Autor: | Fleur O'Hare, Monica L Hu, Thomas L Edwards, Jiang-Hui Wang, Doron G. Hickey, Zhengyang Liu, Lauren N Ayton |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Genetic enhancement
Transgene Leber Congenital Amaurosis Bioinformatics medicine.disease_cause Retina Viral vector 03 medical and health sciences 0302 clinical medicine Retinal Diseases parasitic diseases Retinitis pigmentosa medicine Humans Mutation Retinal pigment epithelium business.industry Australia Genetic Therapy Macular degeneration medicine.disease eye diseases Ophthalmology medicine.anatomical_structure 030221 ophthalmology & optometry business 030217 neurology & neurosurgery Optometry |
| Zdroj: | Clinicalexperimental optometry. 104(4) |
| ISSN: | 1444-0938 |
| Popis: | Inherited retinal diseases (IRDs) comprise a heterogeneous group of genetic disorders affecting the retina. Caused by mutations in over 300 genes, IRDs result in visual impairment due to dysfunction and degeneration of photoreceptors, retinal pigment epithelium, or the choroid. Important photoreceptor IRDs include retinitis pigmentosa and Leber congenital amaurosis. Macular dystrophies include Stargardt and Best disease. Currently, IRDs are largely incurable but the landscape of treatment options is rapidly changing for these diseases which, untreated, result in severe visual impairment and blindness.Advances in DNA delivery to the retina and improved genetic diagnosis of IRDs have led to a new era of research into gene therapy for these vision-threatening disorders. Gene therapy is a compelling approach due to the monogenic nature of most IRDs, with the retina being a favourable target for administering genetic vectors due to its immunoprivileged environment, direct visibility, and multiple methods to assess sensitivity and function. Generally, retinal gene therapy involves a subretinal or intravitreal injection of a viral vector, which infects target cells to deliver a therapeutic gene, or transgene. A gene augmentation strategy introduces a functioning copy of a gene to restore expression of a mutated gene, whereas a gene-editing strategy aims to directly edit and correct the mutation. Common delivery vectors include adeno-associated virus (AAV) and lentivirus.Voretigene neparvovec-rzyl (Luxturna) became the first FDA-approved direct gene therapy in December 2017, and the Australian TGA followed suit in August 2020. More are projected to follow, with clinical trials underway for many other IRDs.This review provides an overview of gene therapy for IRDs, including current progress and challenges. A companion article in this issue details target patient populations for IRD gene therapy, and how optometrists can assist in assessing individuals who may be eligible for current and future therapies. |
| Databáze: | OpenAIRE |
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