Significant advances in gene therapy have enabled exploration of therapies for inherited\nretinal disorders, many of which are in preclinical development or clinical evaluation.\nGene therapy for retinal conditions has led the way in this growing field. The loss of\nretinal ganglion cells (RGCs) is a hallmark of a number of retinal disorders. As the\nfield matures innovations that aid in refining therapies and optimizing efficacy are in\ndemand. Gene therapies under development for RGC-related disorders, when delivered\nwith recombinant adeno associated vectors (AAV), have typically been expressed from\nubiquitous promoter sequences. Here we describe how a novel promoter from the murine\nNefh gene was selected to drive transgene expression in RGCs. The Nefh promoter, in\nan AAV2/2 vector, was shown to drive preferential EGFP expression in murine RGCs in\nvivo following intravitreal injection. In contrast, EGFP expression from a CMV promoter\nwas observed not only in RGCs, but throughout the inner nuclear layer and in amacrine\ncells located within the ganglion cell layer (GCL). Of note, the Nefh promoter sequence is\nsufficiently compact to be readily accommodated in AAV vectors, where transgene size\nrepresents a significant constraint. Moreover, this promoter should in principle provide a\nmore targeted and potentially safer alternative for RGC-directed gene therapies.
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