Back

In vivo mRNA delivery to the lung vascular endothelium by dicationic Charge-Altering Releasable Transporters

AbdElwakil, M.; Ni, J.; Ramsay-Burrough, S.; Hurst, P. J.; McClellan, R.; Khasnavis, S. R.; Jia, Y.; Masud, S. R.; Blake, T. R.; Sallets, A.; Haabeth, O.; Sagiv-Barfi, I.; Czerwinski, D. K.; Levy, R.; Wender, P. A.; Kumar, M. E.; Waymouth, R. M.

2025-04-19 bioengineering
10.1101/2025.04.19.649649 bioRxiv
Show abstract

Endothelial cells (EC) comprise the pulmonary vascular bed and play a significant role in health and disease. Consequently, the EC niche represents an attractive therapeutic target for treating a wide range of pulmonary vascular diseases. We have identified a new class of dicationic Charge-Altering Releasable Transporters. These single-component transporters selectively deliver mRNA to the lung upon intravenous administration without the use of a targeting ligand. Significantly, the number and spatial array of cationic charges within the repeating units of the CART polymer are found to control both mRNA delivery efficacy and tissue tropism. High-resolution imaging revealed efficient mRNA delivery to endothelial cells in pulmonary arteries, veins and capillaries. The selective lung tropism of these new CARTs, coupled with the efficient and tunable synthesis of this new family of CART amphiphiles, represents an enabling platform for research and clinical applications.

Matching journals

The top 9 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.