@article{10.1172/jci.insight.96560, author = {Salvatore Botta AND Nicola de Prisco AND Elena Marrocco AND Mario Renda AND Martina Sofia AND Fabiola Curion AND Maria Laura Bacci AND Domenico Ventrella AND Cathal Wilson AND Carlo Gesualdo AND Settimio Rossi AND Francesca Simonelli AND Enrico Maria Surace}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Targeting and silencing of rhodopsin by ectopic expression of the transcription factor KLF15}, year = {2017}, month = {12}, volume = {2}, url = {https://insight.jci.org/articles/view/96560}, abstract = {The genome-wide activity of transcription factors (TFs) on multiple regulatory elements precludes their use as gene-specific regulators. Here we show that ectopic expression of a TF in a cell-specific context can be used to silence the expression of a specific gene as a therapeutic approach to regulate gene expression in human disease. We selected the TF Krüppel-like factor 15 (KLF15) based on its putative ability to recognize a specific DNA sequence motif present in the rhodopsin (RHO) promoter and its lack of expression in terminally differentiated rod photoreceptors (the RHO-expressing cells). Adeno-associated virus (AAV) vector–mediated ectopic expression of KLF15 in rod photoreceptors of pigs enables Rho silencing with limited genome-wide transcriptional perturbations. Suppression of a RHO mutant allele by KLF15 corrects the phenotype of a mouse model of retinitis pigmentosa with no observed toxicity. Cell-specific-context conditioning of TF activity may prove a novel mode for somatic gene–targeted manipulation.}, number = {24}, doi = {10.1172/jci.insight.96560}, url = {https://doi.org/10.1172/jci.insight.96560}, }