RNA delivery to the corneal endothelium using charge-altering releasable transporters
- 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
2026-08-21
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.