Format

Send to

Choose Destination
Front Neurosci. 2017 Apr 5;11:175. doi: 10.3389/fnins.2017.00175. eCollection 2017.

The CRB1 Complex: Following the Trail of Crumbs to a Feasible Gene Therapy Strategy.

Author information

1
Department of Ophthalmology, Leiden University Medical CenterLeiden, Netherlands.
2
Unité Physiologie de la Reproduction et des Comportements, INRA UMR85, Centre National de la Recherche Scientifique UMR-7247, Institut Français du Cheval et de l'Équitation, Université François RabelaisNouzilly, France.
3
Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and SciencesAmsterdam, Netherlands.

Abstract

Once considered science fiction, gene therapy is rapidly becoming scientific reality, targeting a growing number of the approximately 250 genes linked to hereditary retinal disorders such as retinitis pigmentosa and Leber's congenital amaurosis. Powerful new technologies have emerged, leading to the development of humanized models for testing and screening these therapies, bringing us closer to the goal of personalized medicine. These tools include the ability to differentiate human induced pluripotent stem cells (iPSCs) to create a "retina-in-a-dish" model and the self-formed ectodermal autonomous multi-zone, which can mimic whole eye development. In addition, highly specific gene-editing tools are now available, including the CRISPR/Cas9 system and the recently developed homology-independent targeted integration approach, which allows gene editing in non-dividing cells. Variants in the CRB1 gene have long been associated with retinopathies, and more recently the CRB2 gene has also been shown to have possible clinical relevance with respect to retinopathies. In this review, we discuss the role of the CRB protein complex in patients with retinopathy. In addition, we discuss new opportunities provided by stem cells and gene-editing tools, and we provide insight into how the retinal therapeutic pipeline can be improved. Finally, we discuss the current state of adeno-associated virus-mediated gene therapy and how it can be applied to treat retinopathies associated with mutations in CRB1.

KEYWORDS:

CRISPR; crumbs complex; gene therapy; human iPSC; retinal organoids; retinopathies

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center