Gene augmentation therapy attenuates retinal degeneration in a knockout mouse model of Fam161a retinitis pigmentosa - Eyal Banin and Dror Sharon
Chen Matsevich 1, Prakadeeswari Gopalakrishnan 1, Ning Chang 2, Alexey Obolensky 1, Avigail Beryozkin 1, Manar Salameh 1, Corinne Kostic 2, Dror Sharon 3, Yvan Arsenijevic 4, Eyal Banin 5
Affiliations Expand
- PMID: 37580905
- PMCID: PMC10556223
DOI: 10.1016/j.ymthe.2023.08.011
From gene identification to gene augmentation therapy of FAM161A- the most common cause of retinitis pigmentosa in the Israeli population
Abstract
Photoreceptor cell degeneration and death is the major hallmark of a wide group of human blinding diseases including age-related macular degeneration and inherited retinal diseases such as retinitis pigmentosa. In recent years, inherited retinal diseases have become the "testing ground" for novel therapeutic modalities, including gene and cell-based therapies. Currently there is no available treatment for retinitis pigmentosa caused by FAM161A biallelic pathogenic variants. In this study, we injected an adeno-associated virus encoding for the longer transcript of mFam161a into the subretinal space of P24-P29 Fam161a knockout mice to characterize the safety and efficacy of gene augmentation therapy. Serial in vivo assessment of retinal function and structure at 3, 6, and 8 months of age using the optomotor response test, full-field electroretinography, fundus autofluorescence, and optical coherence tomography imaging as well as ex vivo quantitative histology and immunohistochemical studies revealed a significant structural and functional rescue effect in treated eyes accompanied by expression of the FAM161A protein in photoreceptors. The results of this study may serve as an important step toward future application of gene augmentation therapy in FAM161A-deficient patients by identifying a promising isoform to rescue photoreceptors and their function.