A combinatorial synthetic strategy for developing genome-editing protein-delivery agents targeting mouse retina
Jianye Zhang1, Rafał Hołubowicz1,2, Roman Smidak1
1Gavin Herbert Eye Institute - Brunson Center for Translational Vision Research, Department of Ophthalmology, University of California, Irvine, Irvine, CA, USA.
Nature Communications
|February 7, 2026
Summary
New lipidoids derived from Coomassie brilliant blue (CBB) effectively deliver gene-editing proteins to the eye. This breakthrough advances CRISPR/Cas9 therapies for inherited retinal diseases (IRDs), offering potential for single-dose treatments.
Area of Science:
- Ophthalmology
- Gene Therapy
- Molecular Biology
Background:
- Inherited retinal diseases (IRDs) are a significant cause of blindness.
- CRISPR/Cas9 gene editing holds therapeutic potential for IRDs.
- Safe and efficient ocular delivery of gene editors remains a major hurdle.
Purpose of the Study:
- To develop a novel delivery system for ocular gene editing.
- To evaluate the efficacy of Coomassie brilliant blue (CBB)-derived lipidoids for protein delivery in the retina.
- To assess the potential of CBB-lipidoid-based systems for treating IRDs.
Main Methods:
- Development of CBB-derived lipidoids for protein binding and delivery.
- Subretinal injection of Cre recombinase complexed with CBB-lipidoids in mT/mG mice.
- Utilizing CBB-lipidoids incorporated into liposomes for adenine base editor (ABE) ribonucleoprotein (RNP) delivery in the rd12 mouse model.
Main Results:
- CBB-lipidoids facilitated robust Cre-mediated recombination in retinal pigment epithelium and photoreceptors.
- Liposome-CBB11-RNP complexes demonstrated enhanced delivery efficiency.
- A 120-fold increase in ABE-mediated base editing was observed, restoring retinal function in rd12 mice.
Conclusions:
- CBB-augmented, liposome-RNP systems represent a promising platform for ocular gene editing.
- This technology has the potential to enable precise, in vivo gene editing for IRDs.
- The findings pave the way for developing single-dose precision medicines for inherited retinal diseases.
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