Issue 8, 2021

Engineered ε-decalactone lipomers bypass the liver to selectively in vivo deliver mRNA to the lungs without targeting ligands

Abstract

RNA drugs hold real potential for tackling devastating diseases that are currently resistant to small molecule drugs or monoclonal antibodies. However, since these drugs are unstable in vivo and unable to pass through cellular membranes their clinical realization is limited by their successful delivery to target sites. Herein we report on the design of a combinatorial library of polyester lipomers based on the renewable monomer, ε-decalactone (ε-DL), via organocatalytic ring-opening polymerization for mRNA delivery. The ε-DL lipomers showed a surprisingly efficient ability to target the lungs upon intravenous administration. Interestingly, most of the lipomers achieved functional EGFP expression in the lungs, while minimally transfecting hepatocytes and splenic cells. This simple approach for the design of biodegradable materials has the potential for the clinical translation of genetic medicines for the treatment of lung diseases.

Graphical abstract: Engineered ε-decalactone lipomers bypass the liver to selectively in vivo deliver mRNA to the lungs without targeting ligands

Supplementary files

Article information

Article type
Communication
Submitted
01 Yan 2021
Accepted
04 Kho 2021
First published
07 Kho 2021

Mater. Horiz., 2021,8, 2251-2259

Engineered ε-decalactone lipomers bypass the liver to selectively in vivo deliver mRNA to the lungs without targeting ligands

M. M. Abd Elwakil, T. Gao, T. Isono, Y. Sato, Y. H. A. Elewa, T. Satoh and H. Harashima, Mater. Horiz., 2021, 8, 2251 DOI: 10.1039/D1MH00185J

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements