The effectiveness of gene therapy for Retinitis Pigmentosa is intrinsically linked to the efficiency of the delivery system, known as the vector, which is usually a modified adeno-associated virus (AAV). Current delivery methods, particularly the subretinal injection required for many treatments, are invasive and can only target a limited area of the retina. Therefore, a major focus in the scientific space is on engineering better AAV vectors to improve retinal penetration and coverage.

Researchers are modifying the AAV's outer shell, or capsid, to create "next-generation" vectors that can more effectively reach the target cells, such as photoreceptors, following a less invasive intravitreal injection into the central cavity of the eye. An intravitreal injection is a routine procedure performed in an outpatient setting, and if successful, it would drastically improve the safety profile and accessibility of gene therapy. This crucial work is being driven by innovations in molecular biology and is being adopted by the leading biopharma companies in ophthalmic genetics.

These novel AAV capsids are engineered to be "stealthier," allowing them to bypass the anatomical and cellular barriers within the retina, such as the inner limiting membrane (ILM), to reach the outer retinal layers where the photoreceptors and RPE cells reside. The success of these advanced vector systems will enable the treatment of a much larger area of the retina, which is essential for preserving the peripheral vision that is often first affected in the progression of RP.

FAQ

• What is an AAV vector? It is a modified, non-pathogenic virus used in gene therapy to carry the therapeutic genetic material into the target cells of the retina.

• Why is intravitreal injection preferred over subretinal? Intravitreal injection is a minimally invasive, office-based procedure, whereas subretinal injection is a more complex surgery that carries a higher risk of complications.