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Lookup NU author(s): Dr Adriana BuskinORCiD, Professor Majlinda LakoORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2019 The Author(s)Retinitis pigmentosa (RP) is the most common form of inherited vision loss and is characterized by degeneration of retinal photoreceptor cells and the retinal pigment epithelium (RPE). Mutations in pre-mRNA processing factor 31 (PRPF31) cause dominant RP via haploinsufficiency with incomplete penetrance. There is good evidence that the diverse severity of this disease is a result of differing levels of expression of the wild-type allele among patients. Thus, we hypothesize that PRPF31-related RP will be amenable to treatment by adeno-associated virus (AAV)-mediated gene augmentation therapy. To test this hypothesis, we used induced pluripotent stem cells (iPSCs) with mutations in PRPF31 and differentiated them into RPE cells. The mutant PRPF31 iPSC-RPE cells recapitulate the cellular phenotype associated with the PRPF31 pathology, including defective cell structure, diminished phagocytic function, defects in ciliogenesis, and compromised barrier function. Treatment of the mutant PRPF31 iPSC-RPE cells with AAV-PRPF31 restored normal phagocytosis and cilia formation, and it partially restored structure and barrier function. These results suggest that AAV-based gene therapy targeting RPE cells holds therapeutic promise for patients with PRPF31-related RP.
Author(s): Brydon EM, Bronstein R, Buskin A, Lako M, Pierce EA, Fernandez-Godino R
Publication type: Article
Publication status: Published
Journal: Molecular Therapy - Methods and Clinical Development
Year: 2019
Volume: 15
Pages: 392-402
Print publication date: 13/12/2019
Online publication date: 11/11/2019
Acceptance date: 28/10/2019
Date deposited: 09/12/2019
ISSN (print): 1525-0016
ISSN (electronic): 1525-0024
Publisher: Elsevier
URL: https://doi.org/10.1016/j.omtm.2019.10.014
DOI: 10.1016/j.omtm.2019.10.014
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