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AAV-Mediated Gene Augmentation Therapy Restores Critical Functions in Mutant PRPF31+/− iPSC-Derived RPE Cells

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.

Publication metadata

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


DOI: 10.1016/j.omtm.2019.10.014


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Funder referenceFunder name
1456/1457Fight for Sight
GR595RETINA UK (Formerly known as British Retinitis Pigmentosa Society)