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RNA delivery to the corneal endothelium using charge-altering releasable transporters.

Created on 22 Aug 2026

Authors

Sean K Wang, Zhijian Li, Sahil H Shah, Quincy A Edwards, Richard Bouffard, Elizabeth S Hines, Joel A Imventarza, Sven Korte, Matthew S Lawrence, Euisun Song, Ekram Helmy, Laura Amaya, Nae-Won Kang, David Myung, Miao-Chih Tsai, William J Greenleaf, Robert M Waymouth, Sui Wang, Paul A Wender, Howard Y Chang

Published in

Science advances. Volume 12. Issue 34. Pages eady8161. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

RNA therapies hold tremendous promise for treating genetic eye diseases. However, their development is limited by the lack of non-viral delivery platforms that can target specific ocular cell types. Here, we describe a charge-altering releasable transporter (CART) that delivers RNA selectively to the corneal endothelium, a non-regenerative cell layer whose dysfunction underlies several blinding conditions. We characterize the safety of CART-RNA nanoparticles in mice and show that they facilitate delivery of diverse RNA cargoes to the corneal endothelium, including circular RNA and CRISPR/Cas9. We verify that these nanoparticles can be redosed and apply them to achieve corneal gene editing. We further demonstrate CART transfection of corneal endothelial cells from a human donor in vitro and in a non-human primate in vivo, supporting the feasibility of clinical translation. Our findings establish CARTs as a platform for non-viral gene delivery to the eye, with the potential to treat corneal dystrophies and other vision disorders.

PMID:
42627922
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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