Introduction

Retinal Degenerative Diseases (RDDs) have prominently impacted the human population today.
Their prevalence is problematic as they are the leading cause of blindness. One specific RDD is
Retinitis Pigmentosa (RP): a rare, diverse group of hereditary retinal disorders. A particular case
of RP is caused by autosomal recessive mutations in Interphotoreceptor Matrix Proteoglycan 2
(IMPG2). IMPG2 is expressed by the photoreceptors and found in the interphotoreceptor
matrix (IPM). Disease causing mutations of IMPG2 can be modeled in our lab using human
pluripotent stem (hPSC) cell derived optic vesicles (OVs). To discover novel techniques that
would be widely applicable to a diverse group of diseases we turn to an innovative base editing
technique which utilizes CRISPR/Cas9 in a new way without the creation of double stranded
DNA breaks. We propose a novel CRISPR/Cas9 base editing system to correct disease-causing
IMPG2 mutations in patient-specific stem cell lines. The use of this innovative base editing
technique provides added evidence to support the utility of the CRISPR/CAS9 system as well as
potentiating further research into how this capability may be able to treat a vast array of
genetic diseases, such as RP, that affect many people in today’s society.