ArticleEMBO molecular medicine2011
Zinc-finger-based transcriptional repression of rhodopsin in a model of dominant retinitis pigmentosa.
Article in EMBO molecular medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 72 citations in OpenAlex.
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Gene Therapy for Retinitis Pigmentosa: Current Challenges and New Progress.Biomolecules · 2024Review
- CRISPR/SaCas9-based gene editing rescues photoreceptor degeneration throughout a rhodopsin-associated autosomal dominant retinitis pigmentosa mouse model.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Chemical Epigenetic Regulation of Adeno-Associated Virus Delivered Transgenes.Human gene therapy · 2023Article
- Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development.Pharmaceutics · 2023Review
- Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies.Frontiers in neuroscience · 2023Review
- Gene Therapy for Rhodopsin Mutations.Cold Spring Harbor perspectives in medicine · 2022Article
- New Editing Tools for Gene Therapy in Inherited Retinal Dystrophies.The CRISPR journal · 2022Review
- AAV-CRISPR/Cas9 Gene Editing Preserves Long-Term Vision in the P23H Rat Model of Autosomal Dominant Retinitis Pigmentosa.Pharmaceutics · 2022Article
- CRISPR genome surgery in a novel humanized model for autosomal dominant retinitis pigmentosa.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial.Frontiers in neuroscience · 2022Review
- Gene Therapy for Rhodopsin-associated Autosomal Dominant Retinitis Pigmentosa.International ophthalmology clinics · 2021Article
- Challenging Safety and Efficacy of Retinal Gene Therapies by Retinogenesis.International journal of molecular sciences · 2021Article
- Allele-specific editing ameliorates dominant retinitis pigmentosa in a transgenic mouse model.American journal of human genetics · 2021Article
- Gene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art.Frontiers in medicine · 2021Review
- Calpain Activation Is the Major Cause of Cell Death in Photoreceptors Expressing a Rhodopsin Misfolding Mutation.Molecular neurobiology · 2020Article
- SRD005825 Acts as a Pharmacologic Chaperone of Opsin and Promotes Survival of Photoreceptors in an Animal Model of Autosomal Dominant Retinitis Pigmentosa.Translational vision science & technology · 2019Article
- Genome Editing as a Treatment for the Most Prevalent Causative Genes of Autosomal Dominant Retinitis Pigmentosa.International journal of molecular sciences · 2019Review
- Progress in Gene Therapy for Rhodopsin Autosomal Dominant Retinitis Pigmentosa.Advances in experimental medicine and biology · 2019Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite the recent success of gene-based complementation approaches for genetic recessive traits, the development of therapeutic strategies for gain-of-function mutations poses great challenges. General therapeutic principles to correct these genetic defects mostly rely on post-transcriptional gene regulation (RNA silencing). Engineered zinc-finger (ZF) protein-based repression of transcription may represent a novel approach for treating gain-of-function mutations, although proof-of-concept of this use is still lacking. Here, we generated a series of transcriptional repressors to silence human rhodopsin (hRHO), the gene most abundantly expressed in retinal photoreceptors. The strategy was designed to suppress both the mutated and the wild-type hRHO allele in a mutational-independent fashion, to overcome mutational heterogeneity of autosomal dominant retinitis pigmentosa due to hRHO mutations. Here we demonstrate that ZF proteins promote a robust transcriptional repression of hRHO in a transgenic mouse model of autosomal dominant retinitis pigmentosa. Furthermore, we show that specifically decreasing the mutated human RHO transcript in conjunction with unaltered expression of the endogenous murine Rho gene results in amelioration of disease progression, as demonstrated by significant improvements in retinal morphology and function. This zinc-finger-based mutation-independent approach paves the way towards a 'repression-replacement' strategy, which is expected to facilitate widespread applications in the development of novel therapeutics for a variety of disorders that are due to gain-of-function mutations.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.