Related Experiment Video
Updated: Dec 25, 2025
Ultrahigh Resolution Mouse Optical Coherence Tomography to Aid Intraocular Injection in Retinal Gene Therapy Research
Published on: November 2, 2018
CRISPR Interference-Potential Application in Retinal Disease
Caroline F Peddle1, Lewis E Fry1,2, Michelle E McClements1
1Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 9DU, UK.
Abstract:
The treatment of dominantly inherited retinal diseases requires silencing of the pathogenic allele. RNA interference to suppress gene expression suffers from wide-spread off-target effects, while CRISPR-mediated gene disruption creates permanent changes in the genome. CRISPR interference uses a catalytically inactive 'dead' Cas9 directed by a guide RNA to block transcription of chosen genes without disrupting the DNA. It is highly specific and potentially reversible, increasing its safety profile as a therapy. Pre-clinical studies have demonstrated the versatility of CRISPR interference for gene silencing both in vivo and in ex vivo modification of iPSCs for transplantation. Applying CRISPR interference techniques for the treatment of autosomal dominant inherited retinal diseases is promising but there are few in vivo studies to date. This review details how CRISPR interference might be used to treat retinal diseases and addresses potential challenges for clinical translation.
Insights
CRISPR interference offers a precise and reversible method to silence disease-causing genes in inherited retinal diseases. This gene-editing tool shows promise for developing safer therapies by avoiding permanent genomic alterations.
Area of Science:
- Genetics
- Ophthalmology
- Molecular Biology
Background:
- Dominantly inherited retinal diseases necessitate silencing of pathogenic alleles.
- Current gene silencing methods like RNA interference have off-target effects, and CRISPR-mediated gene disruption causes permanent genomic changes.
Purpose of the Study:
- To review the potential of CRISPR interference (CRISPRi) as a therapeutic strategy for autosomal dominant inherited retinal diseases.
- To discuss the advantages of CRISPRi over existing gene silencing techniques and address challenges for clinical translation.
Main Methods:
- CRISPR interference utilizes a catalytically inactive 'dead' Cas9 protein guided by RNA to block gene transcription without DNA alteration.
- Review of pre-clinical studies demonstrating CRISPRi's efficacy in gene silencing both in vivo and ex vivo.
Main Results:
- CRISPRi is highly specific and potentially reversible, offering a safer therapeutic profile.
- Pre-clinical studies show CRISPRi's versatility for gene silencing in various contexts, including iPSC modification for transplantation.
Conclusions:
- CRISPR interference presents a promising, targeted approach for treating autosomal dominant inherited retinal diseases.
- Further in vivo studies are needed to overcome challenges and advance CRISPRi towards clinical application in ophthalmology.
Related Concept Videos
01:59CRISPR
01:28CRISPR/Cas9 Genome Editing
02:31Homologous Recombination