Ocular Gene Therapy: An Overview of Viral Vectors, Immune Responses, and Future Directions

Abstract

Ocular gene therapy has rapidly advanced from proof-of-concept studies to clinical trials by exploiting the unique advantages of the eye, including its easy accessibility, relative immune privilege, and the ability to use the contralateral eye as a control. An important step forward was achieved with the Food and Drug Administration (FDA) approval of voretigene neparvovec (Luxturna) for the treatment of biallelic RPE65-mutation-associated retinal dystrophies in 2017. Gene therapy is a promising field aimed at treating various inherited and acquired eye diseases. Viral vectors such as adeno-associated virus (AAV) are mainly used to efficiently deliver genes. Despite the immune-privileged status of the eye, viral vector-based therapies can induce immune responses, potentially leading to gene therapy-associated uveitis. Future directions include developing strategies to reduce immune responses while maintaining therapeutic efficacy, optimizing vector selection, and improving delivery techniques. Continued advances in the field of viral vectors, particularly AAV, are expanding the potential applications of gene therapy to treat a variety of ocular diseases. To fully realize the potential of ocular gene therapy, more research and clinical trials are needed to improve these methods, ensure safe and efficient treatments, and ultimately overcome existing obstacles.

Keywords: delivery routes; immune responses; ocular applications; ocular gene therapy; viral vectors.

Figure 1

This figure illustrates the comprehensive landscape of ocular gene therapy using viral vectors. The inner circle represents the three primary types of viral vectors used: Adenovirus, Adeno-Associated Virus (AAV), and Lentivirus. The second circle categorizes the main ocular applications: Retinal Disorders, Corneal Disorders, Glaucoma, and Optic Nerve Disorders. The outermost circle details specific diseases targeted by gene therapy within each category. Created with BioRender.com.