CRISPR editing of anti-anemia drug target rescues independent preclinical models of retinitis pigmentosa.

Autor:	Nolan ND; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Institute of Human Nutrition, Columbia Stem Cell Initiative, New York, NY 10032, USA; Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York, NY 10032, USA., Cui X; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Institute of Human Nutrition, Columbia Stem Cell Initiative, New York, NY 10032, USA; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York, NY 10032, USA., Robbings BM; Department of Biochemistry, The University of Washington, Seattle, WA 98195, USA; Diabetes Institute, The University of Washington, Seattle, WA 98195, USA., Demirkol A; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Institute of Human Nutrition, Columbia Stem Cell Initiative, New York, NY 10032, USA; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York, NY 10032, USA; Vocational School of Health Services, Uskudar University, 34672 Istanbul, Turkey., Pandey K; Department of Biochemistry, The University of Washington, Seattle, WA 98195, USA., Wu WH; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Institute of Human Nutrition, Columbia Stem Cell Initiative, New York, NY 10032, USA; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York, NY 10032, USA., Hu HF; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Institute of Human Nutrition, Columbia Stem Cell Initiative, New York, NY 10032, USA; Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York, NY 10032, USA., Jenny LA; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Institute of Human Nutrition, Columbia Stem Cell Initiative, New York, NY 10032, USA; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York, NY 10032, USA., Lin CS; Herbert Irving Comprehensive Cancer Center, Department of Pathology & Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Departments of Ophthalmology, Pathology & Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA., Hass DT; Department of Biochemistry, The University of Washington, Seattle, WA 98195, USA., Du J; Department of Ophthalmology and Visual Sciences, West Virginia University, Morgantown, WV 26506, USA; Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, WV 26501, USA., Hurley JB; Department of Biochemistry, The University of Washington, Seattle, WA 98195, USA. Electronic address: jbhhh@uw.edu., Tsang SH; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Institute of Human Nutrition, Columbia Stem Cell Initiative, New York, NY 10032, USA; Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA; Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York, NY 10032, USA; Departments of Ophthalmology, Pathology & Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: sht2@columbia.edu.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 Apr 16; Vol. 5 (4), pp. 101459. Date of Electronic Publication: 2024 Mar 21.
DOI:	10.1016/j.xcrm.2024.101459
Abstrakt:	Retinitis pigmentosa (RP) is one of the most common forms of hereditary neurodegeneration. It is caused by one or more of at least 3,100 mutations in over 80 genes that are primarily expressed in rod photoreceptors. In RP, the primary rod-death phase is followed by cone death, regardless of the underlying gene mutation that drove the initial rod degeneration. Dampening the oxidation of glycolytic end products in rod mitochondria enhances cone survival in divergent etiological disease models independent of the underlying rod-specific gene mutations. Therapeutic editing of the prolyl hydroxylase domain-containing protein gene (PHD2, also known as Egln1) in rod photoreceptors led to the sustained survival of both diseased rods and cones in both preclinical autosomal-recessive and dominant RP models. Adeno-associated virus-mediated CRISPR-based therapeutic reprogramming of the aerobic glycolysis node may serve as a gene-agnostic treatment for patients with various forms of RP. Competing Interests: Declaration of interests S.H.T. receives research support from Emendo. He is on the scientific and clinical advisory board for Emendo, Medical Excellence Capital, and Nanoscope Therapeutics. S.H.T. and X.C. hold a patent related to this work: WO2018232227A1. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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