Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Targeting and silencing of rhodopsin by ectopic expression of the transcription factor KLF15
Salvatore Botta, … , Francesca Simonelli, Enrico Maria Surace
Salvatore Botta, … , Francesca Simonelli, Enrico Maria Surace
Published December 21, 2017
Citation Information: JCI Insight. 2017;2(24):e96560. https://doi.org/10.1172/jci.insight.96560.
View: Text | PDF
Research Article Ophthalmology Therapeutics

Targeting and silencing of rhodopsin by ectopic expression of the transcription factor KLF15

  • Text
  • PDF
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.

Authors

Salvatore Botta, Nicola de Prisco, Elena Marrocco, Mario Renda, Martina Sofia, Fabiola Curion, Maria Laura Bacci, Domenico Ventrella, Cathal Wilson, Carlo Gesualdo, Settimio Rossi, Francesca Simonelli, Enrico Maria Surace

×

Full Text PDF | Download (1.95 MB)


Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts