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

Owen S Fenton; Kevin J Kauffman; Rebecca L McClellan; Eric A Appel; J Robert Dorkin; Mark W Tibbitt; Michael W Heartlein; Frank DeRosa; Robert Langer; Daniel G Anderson

doi:10.1002/adma.201505822

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

Adv Mater. 2016 Apr 20;28(15):2939-43. doi: 10.1002/adma.201505822. Epub 2016 Feb 18.

Authors

Owen S Fenton^{1

2}, Kevin J Kauffman^{1

3}, Rebecca L McClellan¹, Eric A Appel¹, J Robert Dorkin^{1

4}, Mark W Tibbitt¹, Michael W Heartlein⁵, Frank DeRosa⁵, Robert Langer^{1

3

6

7}, Daniel G Anderson^{1

3

6

7}

Affiliations

¹ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
² Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
³ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁴ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁵ Shire Pharmaceuticals, Lexington, MA, 02421, USA.
⁶ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁷ Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Alkenes / chemistry*
Amino Alcohols / chemistry*
Biomimetic Materials / chemistry*
Drug Carriers / chemistry*
Erythropoietin / genetics
Humans
Lipids / chemistry*
Nanoparticles / chemistry*
RNA, Messenger / chemistry
RNA, Messenger / genetics

Substances

Alkenes
Amino Alcohols
Drug Carriers
Lipids
RNA, Messenger
Erythropoietin

Abstract

Publication types

MeSH terms

Substances

Grants and funding