Gene Therapy

A process that uses viruses to replace faulty genes in retinal cells with healthy ones in order to stop or slow vision loss from inherited diseases.

Conditions Treated

Retinal gene therapy has achieved significant milestones in treating inherited retinal diseases, such as Leber congenital amaurosis (LCA). In 2017, the FDA approved Luxturna, an AAV-based gene therapy for LCA caused by biallelic RPE65 mutations, marking the first approved gene therapy for an inherited disease in the United States.

Ongoing clinical trials are investigating the use of retinal gene therapy for other conditions, such as retinitis pigmentosa, age-related macular degeneration (AMD), choroideremia and color blindness. These trials aim to assess the safety and efficacy of various AAV-based gene therapy approaches in treating a broader range of retinal disorders.

Future Directions

As the field advances, retinal gene therapy holds the potential to revolutionize the treatment of inherited and acquired retinal diseases, offering hope for patients with previously untreatable forms of blindness.

Gene Therapy

Overview

Retinal gene therapy involves the use of adeno-associated virus (AAV) or other types of viral or nonviral vectors to deliver functional copies of genes to specific cell types within the retina. This approach has shown promise in treating a variety of inherited and non-inherited retinal diseases that cause vision loss or blindness.

AAV vectors are the most widely used delivery systems for retinal gene therapy due to their low immunogenicity, ability to transduce non-dividing cells, and long-term transgene expression. The retina's immune-privileged status further enhances the safety and efficacy of AAV-mediated gene delivery. Since AAVs have a limited capacity to carry small genes, other vectors such as lentivirus or nonviral vectors are considered for the delivery of larger genes.

Mechanism

Retinal gene therapy targets specific cell types, such as retinal pigment epithelium (RPE), photoreceptors, or retinal ganglion cells, depending on the disease being treated. The choice of vector, route of administration (intravitreal or subretinal), and promoter sequence can influence the tropism and expression of the therapeutic gene.

Successful gene therapy requires the delivered transgene to produce a functional protein that can compensate for the defective or missing protein caused by the disease. Modulation of transgene expression may be necessary to maintain long-term therapeutic benefits and avoid potential toxicity.

Challenges

Despite the progress made in retinal gene therapy, several challenges remain. These include optimizing vector design and delivery, improving the specificity and efficiency of transgene expression, and addressing potential immune responses. Researchers are also exploring novel AAV variants and targeting strategies to expand the applications of retinal gene therapy.

Conditions Treated

Retinal gene therapy has achieved significant milestones in treating inherited retinal diseases, such as Leber congenital amaurosis (LCA). In 2017, the FDA approved Luxturna, an AAV-based gene therapy for LCA caused by biallelic RPE65 mutations, marking the first approved gene therapy for an inherited disease in the United States.

Ongoing clinical trials are investigating the use of retinal gene therapy for other conditions, such as retinitis pigmentosa, age-related macular degeneration (AMD), choroideremia and color blindness. These trials aim to assess the safety and efficacy of various AAV-based gene therapy approaches in treating a broader range of retinal disorders.

Future Directions

As the field advances, retinal gene therapy holds the potential to revolutionize the treatment of inherited and acquired retinal diseases, offering hope for patients with previously untreatable forms of blindness.

Overview

Retinal gene therapy involves the use of adeno-associated virus (AAV) or other types of viral or nonviral vectors to deliver functional copies of genes to specific cell types within the retina. This approach has shown promise in treating a variety of inherited and non-inherited retinal diseases that cause vision loss or blindness.

AAV vectors are the most widely used delivery systems for retinal gene therapy due to their low immunogenicity, ability to transduce non-dividing cells, and long-term transgene expression. The retina's immune-privileged status further enhances the safety and efficacy of AAV-mediated gene delivery. Since AAVs have a limited capacity to carry small genes, other vectors such as lentivirus or nonviral vectors are considered for the delivery of larger genes.

Mechanism

Retinal gene therapy targets specific cell types, such as retinal pigment epithelium (RPE), photoreceptors, or retinal ganglion cells, depending on the disease being treated. The choice of vector, route of administration (intravitreal or subretinal), and promoter sequence can influence the tropism and expression of the therapeutic gene.

Successful gene therapy requires the delivered transgene to produce a functional protein that can compensate for the defective or missing protein caused by the disease. Modulation of transgene expression may be necessary to maintain long-term therapeutic benefits and avoid potential toxicity.

Challenges

Despite the progress made in retinal gene therapy, several challenges remain. These include optimizing vector design and delivery, improving the specificity and efficiency of transgene expression, and addressing potential immune responses. Researchers are also exploring novel AAV variants and targeting strategies to expand the applications of retinal gene therapy.

Conditions Treated

Retinal gene therapy has achieved significant milestones in treating inherited retinal diseases, such as Leber congenital amaurosis (LCA). In 2017, the FDA approved Luxturna, an AAV-based gene therapy for LCA caused by biallelic RPE65 mutations, marking the first approved gene therapy for an inherited disease in the United States.

Ongoing clinical trials are investigating the use of retinal gene therapy for other conditions, such as retinitis pigmentosa, age-related macular degeneration (AMD), choroideremia and color blindness. These trials aim to assess the safety and efficacy of various AAV-based gene therapy approaches in treating a broader range of retinal disorders.

Future Directions

As the field advances, retinal gene therapy holds the potential to revolutionize the treatment of inherited and acquired retinal diseases, offering hope for patients with previously untreatable forms of blindness.

Overview

Retinal gene therapy involves the use of adeno-associated virus (AAV) or other types of viral or nonviral vectors to deliver functional copies of genes to specific cell types within the retina. This approach has shown promise in treating a variety of inherited and non-inherited retinal diseases that cause vision loss or blindness.

AAV vectors are the most widely used delivery systems for retinal gene therapy due to their low immunogenicity, ability to transduce non-dividing cells, and long-term transgene expression. The retina's immune-privileged status further enhances the safety and efficacy of AAV-mediated gene delivery. Since AAVs have a limited capacity to carry small genes, other vectors such as lentivirus or nonviral vectors are considered for the delivery of larger genes.

Mechanism

Retinal gene therapy targets specific cell types, such as retinal pigment epithelium (RPE), photoreceptors, or retinal ganglion cells, depending on the disease being treated. The choice of vector, route of administration (intravitreal or subretinal), and promoter sequence can influence the tropism and expression of the therapeutic gene.

Successful gene therapy requires the delivered transgene to produce a functional protein that can compensate for the defective or missing protein caused by the disease. Modulation of transgene expression may be necessary to maintain long-term therapeutic benefits and avoid potential toxicity.

Challenges

Despite the progress made in retinal gene therapy, several challenges remain. These include optimizing vector design and delivery, improving the specificity and efficiency of transgene expression, and addressing potential immune responses. Researchers are also exploring novel AAV variants and targeting strategies to expand the applications of retinal gene therapy.