Data from: A combinatorial synthetic strategy for developing genome-editing protein-delivery agents targeting mouse retina

Jianye Zhang; Rafał Hołubowicz; Roman Šmidák; Yulun Hu; Samuel W. Du; Jiin Felgner; Grażyna Palczewska; Carolline Rodrigues Menezes; Eleonora Risaliti; Zhiqian Dong; Xiuli Ma; Mojtaba Shayegan; Paul Chen; Li Xing; Maria Holubowicz; B. Li; David Liu; PL Felgner; Gregory P. Tochtrop; Krzysztof Palczewski

doi:10.5061/dryad.d51c5b0hd

Data from: A combinatorial synthetic strategy for developing genome-editing protein-delivery agents targeting mouse retina

Jianye Zhang(University of California, Irvine), Rafał Hołubowicz(University of California, Irvine), Roman Šmidák(University of California, Irvine), Yulun Hu(Case Western Reserve University), Samuel W. Du(University of California, Irvine), Jiin Felgner(University of California, Irvine), Grażyna Palczewska(University of California, Irvine), Carolline Rodrigues Menezes(University of California, Irvine), Eleonora Risaliti(University of California, Irvine), Zhiqian Dong(University of California, Irvine), Xiuli Ma(University of California, Irvine), Mojtaba Shayegan(Case Western Reserve University), Paul Chen(Broad Institute), Li Xing(University of California, Irvine), Maria Holubowicz(University of California, Irvine), B. Li(Case Western Reserve University), David Liu(Broad Institute), PL Felgner(University of California, Irvine), Gregory P. Tochtrop(Case Western Reserve University), Krzysztof Palczewski(University of California, Irvine)

Open MIND

December 20, 2025

10.5061/dryad.d51c5b0hd

Cited by 1Open Access

Abstract

CRISPR/Cas9-based gene-editing technologies offer promise for treating inherited retinal diseases (IRDs); however, safe and efficient ocular delivery of precision editors remains challenging. To address this challenge, we report a new class of Coomassie brilliant blue (CBB)-derived lipidoids that bind and deliver proteins. Subretinal injection of Cre complexed with these lipidoids into mT/mG mice leads to robust recombination in the retinal pigment epithelium and photoreceptors. We employ the CBB-lipidoid platform to deliver adenine base editor (ABE) ribonucleoproteins (RNP). Incorporating CBB lipidoids into liposomes improves delivery efficiency. CBB11 stands out for facilitating precise in vivo ABE-mediated gene editing. Delivery of liposome-CBB11-RNP complexes results in a 120-fold increase in base editing compared to RNP alone and restores the scotopic ERG b-wave response in the rd12 mouse model. These results demonstrate the potential of CBB-augmented, liposome-RNP systems for therapeutic gene editing in the eye, paving the way for single-dose precision medicines to treat IRDs.

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