ArticleMolecular therapy. Nucleic acids2025
Design of bifunctional RNA-binding compounds that can modulate siRNA hydrophobicity for deep penetration and gene silencing in the retina.
Article in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Small interfering RNA (siRNA) could be a promising new modality to block the neovascularization in retinal diseases. For ocular siRNA delivery, hydrophobic modification is essential to increase the siRNA membrane compatibility, self-deliverability, and retinal penetration. Current covalent approach such as cholesterol or fatty acid conjugation can only tether one hydrophobic ligand to siRNA molecule, which shows limitations in the ocular delivery. Here, we identified a siRNA-binding drug, quinacrine, and conjugated it with cholesterol to obtain a bifunctional RNA-binding compound that can act as a tag to tether multiple cholesterol molecules on siRNA non-covalently. Despite a moderate affinity to siRNA (K
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