@article {1478321, title = {AAV-Mediated Gene Augmentation Therapy Restores Critical Functions in Mutant PRPF31 iPSC-Derived RPE Cells}, journal = {Mol Ther Methods Clin Dev}, volume = {15}, year = {2019}, month = {2019 Dec 13}, pages = {392-402}, abstract = {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 () 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 -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 and differentiated them into RPE cells. The mutant 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 iPSC-RPE cells with AAV- 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 -related RP.}, issn = {2329-0501}, doi = {10.1016/j.omtm.2019.10.014}, author = {Brydon, Elizabeth M and Bronstein, Revital and Buskin, Adriana and Lako, Majlinda and Pierce, Eric A and Fernandez-Godino, Rosario} }