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CRISPR/Cas-Mediated Gene Activation as a Versatile Tool for Treatment of Inherited Retinal Dystrophies
David Manuel Mittas1, Zoran Gavrilov2, Emina Ucambarlic2
1Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität Munich, Munich, Germany.
Abstract:
CRISPR/Cas-mediated genome editing is an effective and attractive tool for the treatment of diseases or genes that cannot be adequately covered by gene replacement strategies. The first FDA-approved AAV-vector- and CRISPR/Cas-based clinical trials were each designed for the treatment of a subtype of an inherited retinal dystrophy, underscoring the importance of ophthalmic diseases in the field of gene (editing) therapies. This and most other pre-clinical therapeutic CRISPR/Cas approaches are typically designed for the treatment of single mutations. For the treatment of larger patient cohorts, however, mutation- or ideally gene-independent approaches appear to be more suitable. CRISPR/Cas-mediated transcriptional activation of genes (CRISPRa) is a promising approach to achieve these ambitious goals. In this minireview, focusing on inherited retinal dystrophies, we will discuss recent developments, advantages and limitations, and future prospects of CRISPRa as a therapeutic tool.
Insights
CRISPR transcriptional activation (CRISPRa) offers a promising gene-independent approach for treating inherited retinal dystrophies. This method advances beyond single-mutation therapies for broader patient application.
Area of Science:
- Genetics
- Molecular Biology
- Ophthalmology
Background:
- CRISPR/Cas genome editing shows promise for treating genetic diseases, particularly inherited retinal dystrophies.
- Current preclinical CRISPR/Cas therapies often target single mutations, limiting broader application.
- Gene replacement strategies have limitations for certain genetic defects.
Purpose of the Study:
- To review recent advancements in CRISPR-mediated transcriptional activation (CRISPRa) for inherited retinal dystrophies.
- To discuss the advantages and limitations of CRISPRa as a therapeutic tool in ophthalmology.
- To explore future prospects of CRISPRa for treating a wider range of retinal dystrophies.
Main Methods:
- Review of current literature on CRISPR/Cas and CRISPRa applications in inherited retinal dystrophies.
- Analysis of preclinical studies and clinical trial designs.
- Discussion of mutation- or gene-independent therapeutic strategies.
Main Results:
- CRISPRa presents a viable strategy for gene-independent therapeutic approaches in retinal dystrophies.
- This method overcomes limitations of single-mutation targeting and gene replacement.
- Early clinical trials highlight the significance of gene editing in ophthalmic diseases.
Conclusions:
- CRISPRa is a powerful tool for developing broad-acting therapies for inherited retinal dystrophies.
- Further research is needed to optimize CRISPRa delivery and efficacy for clinical translation.
- CRISPRa holds significant potential for advancing gene-based treatments in ophthalmology.
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