PRPF31-retinitis pigmentosa: Challenges and opportunities for clinical translation.

ABSTRACT

Mutations in pre-mRNA processing factor 31 cause autosomal dominant retinitis pigmentosa (PRPF31-RP), for which there is currently no efficient treatment, making this disease a prime target for the development of novel therapeutic strategies. PRPF31-RP exhibits incomplete penetrance due to haploinsufficiency, in which reduced levels of gene expression from the mutated allele result in disease. A variety of model systems have been used in the investigation of disease etiology and therapy development. In this review, we discuss recent advances in both in vivo and in vitro model systems, evaluating their advantages and limitations in the context of therapy development for PRPF31-RP. Additionally, we describe the latest approaches for treatment, including AAV-mediated gene augmentation, genome editing, and late-stage therapies such as optogenetics, cell transplantation, and retinal prostheses.