Journal
NANOSCALE
Volume 11, Issue 18, Pages 9023-9031Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c9nr02004g
Keywords
-
Categories
Funding
- Canadian Institutes of Health Research [FDN 148469]
- British Columbia Innovation Council Ignite grant
- Swiss National Science Foundation (SNF, Early Postdoc. Mobility Fellowship) [174975]
- VENI Fellowship from the Netherlands Organization for Scientific Research (NWO). [14385]
- SNF Sinergia grant [180257]
Ask authors/readers for more resources
The success of Onpattro (patisiran) clearly demonstrates the utility of lipid nanoparticle (LNP) systems for enabling gene therapies. These systems are composed of ionizable cationic lipids, phospholipid, cholesterol, and polyethylene glycol (PEG)-lipids, and are produced through rapid-mixing of an ethanolic-lipid solution with an acidic aqueous solution followed by dialysis into neutralizing buffer. A detailed understanding of the mechanism of LNP formation is crucial to improving LNP design. Here we use cryogenic transmission electron microscopy and fluorescence techniques to further demonstrate that LNP are formed through the fusion of precursor, pH-sensitive liposomes into large electron-dense core structures as the pH is neutralized. Next, we show that the fusion process is limited by the accumulation of PEG-lipid on the emerging particle. Finally, we show that the fusion-dependent mechanism of formation also applies to LNP containing macromolecular payloads including mRNA, DNA vectors, and gold nanoparticles.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available