Correcting photoreceptor diseases at their source: CRISPR strategies for cone-rod dystrophy and achromatopsia.
Haniya Fatima Zaki, Jamaalia Bishri, Mariam Abdul Muqtadir et al.
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In 30 seconds
This systematic review evaluates CRISPR/Cas9 strategies for treating cone-rod dystrophy (CORD) and achromatopsia (ACHM) by analyzing preclinical studies. The review found that in vivo editing achieved approximately 8-45% on-target efficiency in mice and 13% in macaques. Notably, a dual-AAV strategy preserved outer nuclear layer thickness for up to 24 weeks in CORD6 mice.
Key findings
- In vivo studies achieved approximately 8-45% on-target editing in mice and 13% in macaques.
- A dual-AAV 'ablate-and-replace' strategy preserved outer nuclear layer thickness for up to 24 weeks in CORD6 mice.
- In vitro, SpCas9-HiFi-mediated PDE6C correction in ACHM iPSCs achieved approximately 80% editing efficiency.
Why it matters
The potential of CRISPR/Cas9 for precise gene correction in inherited retinal diseases could transform treatment approaches, particularly for conditions with current therapeutic limitations. Understanding these strategies is crucial for future clinical applications.
What to keep in mind
Safety data were limited, with immune responses assessed in only one primate study.