Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Apr 20;28(15):2939-43.
doi: 10.1002/adma.201505822. Epub 2016 Feb 18.

Bioinspired Alkenyl Amino Alcohol Ionizable Lipid Materials for Highly Potent In Vivo mRNA Delivery

Owen S Fenton  1   2 , Kevin J Kauffman  1   3 , Rebecca L McClellan  1 , Eric A Appel  1 , J Robert Dorkin  1   4 , Mark W Tibbitt  1 , Michael W Heartlein  5 , Frank DeRosa  5 , Robert Langer  1   3   6   7 , Daniel G Anderson  1   3   6   7
Affiliations

Bioinspired Alkenyl Amino Alcohol Ionizable Lipid Materials for Highly Potent In Vivo mRNA Delivery

Owen S Fenton et al. Adv Mater. .

Abstract

Thousands of human diseases could be treated by selectively controlling the expression of specific proteins in vivo. A new series of alkenyl amino alcohol (AAA) ionizable lipid nanoparticles (LNPs) capable of delivering human mRNA with unprecedented levels of in vivo efficacy is demonstrated. This study highlights the importance of utilizing synthesis tools in tandem with biological inspiration to understand and improve nucleic acid delivery in vivo.

Keywords: RNA; biomaterials; drug delivery; nanoparticles; proteins.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Naturally occurring components of the cell membrane contain alkenyl amino alcohol (AAA) functionality serving as the inspiration for the development of AAA ionizable lipids. These lipids form the basis of lipid nanoparticles exhibiting highly efficient in vivo delivery of mRNA.
Figure 2
Figure 2
a) Synthesis of OF-00 through OF-03, seminal members of the AAA class of ionizable lipids. b) Representative cryogenic transmission electron microscopy of OF-02 LNPs.
Figure 3
Figure 3
a) In vivo expression of EPO following administration of AAA LNPs for delivery of mRNA. b) Batch-to-batch variability of OF-02 LNPs for EPO mRNA delivery in vivo. c) In vivo dose response curves for OF-02 and cKK-E12 LNPs. d) EPO expression following administration of OF-02 and cKK-E12 LNPs at 6 and 24 h. Data presented as mean + standard deviation (n = 3).
Figure 4
Figure 4
Representative luminescence biodistribution of a) cKK-E12 and b) OF-02 LNPs with luciferase mRNA ex-vivo and c) associated quantification. Data presented as mean + standard deviation (n = 3).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kanasty R, Dorkin JR, Vegas A, Anderson D. Nat Mater. 2013;12:967–977. - PubMed
    2. Whitehead KA, Langer R, Anderson DG. Nat Rev Drug Discov. 2009;8:516–516. - PMC - PubMed
    1. Sahin U, Kariko K, Tureci O. Nat Rev Drug Discov. 2014;13:759–780. - PubMed
    1. Leader B, Baca QJ, Golan DE. Nat Rev Drug Discov. 2008;7:21–39. - PubMed
    1. Kormann MSD, Hasenpusch G, Aneja MK, Nica G, Flemmer AW, Herber-Jonat S, Huppmann M, Mays LE, Illenyi M, Schams A, Griese M, Bittmann I, Handgretinger R, Hartl D, Rosenecker J, Rudolph C. Nat Biotechnol. 2011;29:154–U196. - PubMed
    1. Thess A, Grund S, Mui BL, Hope MJ, Baumhof P, Fotin-Mleczek M, Schlake T. Mol Ther. 2015;23:S55–S55. - PMC - PubMed

Publication types