Modern Genetic Technologies for the Treatment of Stargardt Syndrome. Part 1. Non-viral Methods OF Delivery of Therapeutic Constructs

Stargardt disease (STGD1) is the most common type of inherited macular degeneration. It is an autosomal recessive disorder caused by pathogenic variants in the ABCA4 gene, which encodes a transmembrane protein of the ATP-binding cassette transporter. This protein is located in the outer segments of photoreceptors and is essential for retinal recycling. Dysfunction of the ABCA4 transporter leads to the accumulation of toxic vitamin A metabolites in retinal pigment epithelial cells and subsequent photoreceptor degeneration. Recently, fundamental and translational studies on the molecular pathophysiology of inherited retinal diseases, including Stargardt disease, have significantly improved the understanding of their mechanisms, leading to the stimulation and development of new therapeutic strategies. The purpose of this review is to describe current approaches aimed at correcting the genetic defect in STGD1 and to analyze their advantages and limitations in terms of potential clinical use. The first part of the review examines non-viral gene therapy technologies as applied to the treatment of Stargardt disease.

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