CRISPR-based gene editing for Choroideremia

Most clinical trials for retinal gene therapies, including our Choroideremia study (NCT01461213), have focused on gene supplementation mediated by adeno-associated viruses (AAVs). While this approach has shown therapeutic potential, it comes with notable limitations. Gene supplementation is applicable only to recessive genetic disorders, and its long-term efficacy remains controversial, with some follow-up studies documenting relapses in visual function after treatment. Furthermore, AAV vectors face critical challenges such as limited packaging capacity, high production costs, and immunogenicity.
CRISPR-based gene editing technologies offer a transformative alternative for the permanent correction of virtually any disease-causing mutation. Among these tools, prime editing stands out for its precision and versatility, enabling targeted introduction of small insertions, small deletions, and all 12 possible single-base substitutions.
In this project, we are applying prime editing to correct multiple mutations causing Choroideremia, employing cellular, mouse, and zebrafish disease models. To overcome the limitations of AAVs, we are exploring lipid nanoparticle-based delivery of mRNA encoding the prime editing components, aiming for a safer and more cost-efficient approach to gene correction.