Precision gene therapy: Tailoring rAAV-mediated gene therapies for inherited retinal dystrophies (IRDs)

Inherited retinal dystrophies (IRDs) are a heterogeneous group of rare genetic disorders that affect multiple retinal cell types, including photoreceptors, Müller glia, bipolar cells, retinal ganglion cells (RGCs), and the retinal pigment epithelium (RPE). Recombinant adeno-associated viruses (rAAVs) have emerged as the leading vectors for gene delivery in the retina due to their safety profile and ability to drive long-term expression. However, achieving precise cell targeting and appropriate transgene regulation remains a key challenge. Recent advances in capsid engineering and the discovery of cell-type-specific regulatory elements have opened new avenues for improving the precision of rAAV-mediated therapies. These refined tools can be integrated with various therapeutic strategies, such as gene augmentation, genome editing, RNA modulation, and optogenetics, to expand the range and effectiveness of treatments for IRDs. This review focuses on recent developments in the customization of rAAV vectors to achieve cell-specific gene therapy for IRDs.