Mutation Specific Treatments for Inherited Retinal Diseases

The next frontier in genetic therapy for IRDs is the correction or silencing of specific mutations. This is of relevance to conditions with dominant negative and gain-of-function disease mechanisms, or with causative genes that are too large for gene replacement using AAV vectors. We discuss two approaches that have reached the stage of human clinical trials: CRISPR-Cas9 based gene editing and post-transcriptional gene silencing using antisense oligonucleotides. Other mutation-specific treatment approaches in pre-clinical development include adenosine deaminases acting on RNA (ADAR)-based RNA editing, RNA interference, and translational read through inducing drugs (TRADs). These have been reviewed elsewhere (e.g., Martinez Velazquez and Ballios 2021).