Abstract
Inherited retinal diseases (IRDs) encompass a large heterogeneous group of rare blinding disorders whose etiology originates from mutations in the 280 genes identified to date. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems represent a promising avenue for the treatment of IRDs, as exemplified by FDA clinical trial approval of EDIT-101 (AGN-151587), which removes a deep intronic variant in the CEP290 gene that causes Leber congenital amaurosis (LCA) type 10. Prime editing is a novel double-strand break (DSB) independent CRISPR/Cas system which has the potential to correct all 12 possible transition and transversion mutations in addition to small deletions and insertions. Here, as a proof-of-concept study, we describe a methodology using prime editing for the in vitro installation and correction of the classical Pde6brd10 c.1678C > T (p.Arg560Cys) mutation which causes autosomal recessive retinitis pigmentosa (RP) in mice.
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Acknowledgement
B.L.D.C. is a recipient of the Capes PhD scholarship. S.H.T. and Jonas Children's Vision Care is supported by the National Institute of Health 5P30CA013696, U01 EY030580, U54OD020351, R24EY028758, R24EY027285, 5P30EY019007, R01EY018213, R01EY024698, R01EY026682, R21AG050437, the Schneeweiss Stem Cell Fund, New York State [SDHDOH01-C32590GG-3450000], the Foundation Fighting Blindness New York Regional Research Center Grant [TA-NMT-0116-0692-COLU], Nancy & Kobi Karp, the Crowley Family Funds, The Rosenbaum Family Foundation, Alcon Research Institute, the Gebroe Family Foundation, the Research to Prevent Blindness (RPB) Physician-Scientist Award, unrestricted funds from RPB, New York, NY, USA. P.M.J.Q. is the current recipient of a Curing Retinal Blindness Foundation (CRBF) grant, a Knights Templar Eye Foundation (KTEF) Career Starter grant, the International Retinal Research Foundation (IRRF) Loris and David Rich Postdoctoral Scholar Award and a New York Stem Cell Foundation (NYSCF)—Druckenmiller Fellowship.
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Stephen H. Tsang receives financial support from Abeona Therapeutics, Inc and Emendo. He is also the founder of Rejuvitas and is on the scientific and clinical advisory board for Nanoscope Therapeutics. Peter M.J. Quinn receives research support from Rejuvitas, Inc.
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Tsai, YT. et al. (2023). Prime Editing for the Installation and Correction of Mutations Causing Inherited Retinal Disease: A Brief Methodology. In: Tsang, S.H., Quinn, P.M. (eds) Retinitis Pigmentosa. Methods in Molecular Biology, vol 2560. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2651-1_29
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DOI: https://doi.org/10.1007/978-1-0716-2651-1_29
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