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Prime Editing Strategy to Install the PRPH2 c.828+1G>A Mutation

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Retinal Degenerative Diseases XIX

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1415))

Abstract

Mutations in peripherin 2 (PRPH2) are associated with a spectrum of inherited retinal diseases (IRDs) including retinitis pigmentosa (RP) and macular degeneration. As PRPH2 is localized to cone and rod outer segments, mutations in PRPH2 lead the disorganization or absence of photoreceptor outer segments. Here, we report on a patient with PRPH2-linked RP who exhibited widespread RPE atrophy with a central area of macular atrophy sparing the fovea. In future studies, we plan to model the pathobiology of PRPH2-based RP using induced pluripotent stem cell (iPSC)-derived retinal organoids. To effectively model rare mutations using iPSC-derived retinal organoids, we first require a strategy that can install the desired mutation in healthy wild-type iPSC, which can efficiently generate well-laminated retinal organoids. In this study, we developed an efficient prime editing strategy for the installation of the pathogenic PRPH2 c.828+1 G>A splice-site mutation underlying our patient’s disease.

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Acknowledgments

SHT and The Jonas Children’s Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory are supported by the National Institutes of Health [P30EY019007, R01EY018213, R01EY024698, R01EY026682, R24EY027285, U01EY030580], National Cancer Institute Core [5P30CA013696], Foundation Fighting Blindness [TA-NMT-0116-0692-COLU], the Research to Prevent Blindness (RPB) Physician-Scientist Award. BLD is a recipient of the Capes PhD scholarship. PMJQ is the current recipient of a Curing Retinal Blindness Foundation (CRBF) grant, a Knights Templar Eye Foundation (KTEF) Career Starter grant, an Uplifting Athletes Young Investigator grant, and a New York Stem Cell Foundation (NYSCF) – Druckenmiller Fellowship.

Conflict of Interest

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.

Author information

Author notes

  1. Authors Salvatore Marco Caruso, Yi-Ting Tsai and Bruna Lopes da Costa have equally contributed to this chapter.

Authors and Affiliations

  1. Department of Biomedical Engineering, Columbia University, New York, NY, USA

    Salvatore Marco Caruso, Yi-Ting Tsai, Bruna Lopes da Costa & Stephen H. Tsang

  2. Edward S. Harkness Eye Institute, Department of Ophthalmology, Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, NY, USA

    Salvatore Marco Caruso, Bruna Lopes da Costa, Masha Kolesnikova, Laura A. Jenny, Stephen H. Tsang & Peter M. J. Quinn

  3. Jonas Children’s Vision Care, and Bernard & Shirlee Brown Glaucoma Laboratory, Department of Ophthalmology, Columbia University, New York, NY, USA

    Salvatore Marco Caruso, Bruna Lopes da Costa, Masha Kolesnikova, Laura A. Jenny, Stephen H. Tsang & Peter M. J. Quinn

  4. Columbia Stem Cell Initiative, Columbia University, New York, NY, USA

    Stephen H. Tsang

  5. Department of Pathology & Cell Biology, Columbia University, New York, NY, USA

    Stephen H. Tsang

  6. Institute of Human Nutrition, Columbia University, New York, NY, USA

    Stephen H. Tsang

Authors
  1. Salvatore Marco Caruso
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  2. Yi-Ting Tsai
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  3. Bruna Lopes da Costa
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  4. Masha Kolesnikova
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  5. Laura A. Jenny
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  6. Stephen H. Tsang
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  7. Peter M. J. Quinn
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Corresponding author

Correspondence to Peter M. J. Quinn .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    John D. Ash

  2. Ocular Genomics InstituteDepartment of OphthalmologyMassachusetts Eye and Ear InfirmaryHarvard Medical School, Boston, MA, USA

    Eric Pierce

  3. Health Sciences Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Robert E. Anderson

  4. Department of Ophthalmology, Duke Medical Center, Durham, NC, USA

    Catherine Bowes Rickman

  5. Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA

    Joe G. Hollyfield

  6. Laboratory for Retinal Cell BiologyDepartment of OphthalmologyUniversity Hospital Zurich, University of Zurich, Schlieren, Switzerland

    Christian Grimm

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© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

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Cite this paper

Caruso, S.M. et al. (2023). Prime Editing Strategy to Install the PRPH2 c.828+1G>A Mutation. In: Ash, J.D., Pierce, E., Anderson, R.E., Bowes Rickman, C., Hollyfield, J.G., Grimm, C. (eds) Retinal Degenerative Diseases XIX. Advances in Experimental Medicine and Biology, vol 1415. Springer, Cham. https://doi.org/10.1007/978-3-031-27681-1_15

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