Gene therapy advances using canine and feline animal models of inherited retinal degeneration

TL;DR

This paper reviews how gene therapy for inherited retinal diseases has advanced using dog and cat models, highlighting their role in developing human treatments.

Contribution

The paper provides a comprehensive review of canine and feline models used in preclinical gene therapy studies for inherited retinal degenerations.

Findings

Canine and feline models of inherited retinal degeneration are homologous to human diseases and have been used in successful preclinical trials.

AAV-based gene delivery is a safe and effective method for gene therapy in these animal models prior to human clinical trials.

Both recessive and dominant forms of retinal diseases have been addressed using these models, offering insights into diverse therapeutic strategies.

Abstract

Inherited retinal degenerations (IRDs) are a genetically heterogenous group of visually impairing conditions that affect many people worldwide. They are caused by mutations in a variety of genes with a range of vision loss onset from childhood to middle-age. Many IRDs are inherited in an autosomal recessive fashion and are due to loss of function of the gene product, allowing for a standard gene augmentation approach in which a normal copy of the mutated gene is introduced. Retinal gene delivery using adeno-associated viral (AAV) vectors has proven to be the safest and most effective approach and has been used in many clinical trials. Introducing a normal copy of the mutated gene is applicable when used prior to advanced photoreceptor degeneration while there are still sufficient “rescuable” photoreceptors. Several naturally occurring IRDs which are homologous to human IRDs have been identified in the dog and cat. A subset of these has been successfully used for preclinical trials that have contributed to regulatory approval for subsequent human clinical trials. While most have been for recessive conditions due to loss of gene function, examples of dominant disease requiring a knockdown of the mutant transcript exist and have been used. IRDs bear a considerable economic and societal impact. Identification and familiarity with appropriate models that can lead to successful therapeutic approaches are of great significance. This narrative review aims to summarize advances in gene therapy using canine and feline models for human IRDs and discuss their advantages and disadvantages as well as future perspectives using them.

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