Uses
306-N16B is a selective lung-targeted lipid nanoparticle that reversibly targets lung endothelial cells and specific immune cells through selective adsorption of a protein corona mediated by differences in tail structure (such as fibrinogen β/γ chain). 306-N16B binds to specific plasma proteins in the blood to form a protein corona, which guides the particles to be enriched in the lungs, releases mRNA and promotes target cell gene expression, exerts efficient lung cell transfection activity, and can precisely regulate gene delivery of different cell types in the lungs (such as endothelial cells and macrophages). 306-N16B can be used in gene therapy technologies for hereditary lung diseases including pulmonary lymphangioleiomyomatosis (LAM), restoring tumor suppressor function by delivering Tsc2 mRNA, and can also be used for lung-specific mRNA vaccines and gene editing therapies[1][2].
in vivo
In the in vivo fluorescence imaging experiment of mice, 306-N16B (0.5 mg/kg mRNA; 6 h) is significantly enriched in the lungs and efficiently expressed luciferase, while the signals in other organs such as the liver and spleen were weak, proving its lung-targeted delivery ability[1].
In the Cre/LoxP gene editing experiment, 306-N16B (0.75 mg mRNA equiv./kg; 7 d) induces Ai14 mouse lung endothelial cell-specific tdTomato expression, and flow cytometry shows that the endothelial cell transfection rate reached 33.6%, which is significantly higher than that of epithelial cells (1.5%) and macrophages (1.9%)[1].
References
[1] Qiu M, et al. Lung-selective mRNA delivery of synthetic lipid nanoparticles for the treatment of pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. 2022 Feb 22;119(8):e2116271119. DOI:
10.1073/pnas.2116271119[2] Yuan Z, et al. Impact of physicochemical properties on biological effects of lipid nanoparticles: Are they completely safe. Sci Total Environ. 2024 Jun 1;927:172240. DOI:
10.1016/j.scitotenv.2024.172240
