Dr. Raulas Krusnauskas from Harvard Medical School Awarded $90,000 Knights Templar Eye Foundation Grant for Inherited Retinal Degenerations Research

Dr. Raulas Krusnauskas from Massachusetts Eye and Ear, Ocular Genomics Institute, Harvard Medical School located in Boston, Massachusetts was awarded a $90,000 grant for the research entitled: Proof of concept for twin prime editing of RP1 mutations for inherited retinal degenerations.

Vision relies on the efficient conversion of light entering the eye into electrical signals by specialized cells of the retina - photoreceptors. These electrical signals later travel to the brain to be interpreted by the visual cortex. Described process is termed phototransduction and involves the sequential activation of a series of signaling proteins. Mutations that result in defective proteins are a leading cause of inherited retinal degenerations (IRDs). IRDs show multiple inheritance patterns and show either early or later onset. Some success for treatment of Leber congenital amaurosis was with AAV based therapy for RPE65. However, AAV packaging limitations precludes similar strategies for the majority of the IRD genes, like RP1. RP1 gene encodes a protein that localizes at the axoneme of the photoreceptor outer segment, where it is required for appropriate orientation and stacking of outer segment disks to ensure normal vision. CRISPR technologies enable genome editing by inducing double strand breaks (DBS) in DNA and causing non-homologous end joining. Improvements in CRISPR led to site specific and DBS free genome editing in the form of base (BE) and prime (PE) editing. PE was further developed into twinPE. In contrast to PE, twinPE uses two epegRNAs, which enable editors to repair many different mutations within a genomic fragment, hence benefiting a larger number of IRD patients. Dr. Krusnauskas will use RP1 gene as an example to evaluate the therapeutic potential of twinPE approach for treating IRDs.