Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs.
Therapeutic nucleic acids hold great promise for the treatment of disease but require vectors for safe and effective delivery. Synthetic nanoparticle vectors composed of poly(β-amino esters) (PBAEs) and nucleic acids have previously demonstrated potential utility for local delivery applications. To expand this potential utility to include systemic delivery of mRNA, hybrid polymer-lipid nanoformulations for systemic delivery to the lungs were developed. Through coformulation of PBAEs with lipid-polyethylene glycol (PEG), mRNA formulations were developed with increased serum stability and increased in vitro potency. The formulations were capable of functional delivery of mRNA to the lungs after intravenous administration in mice. To our knowledge, this is the first report of the systemic administration of mRNA for delivery to the lungs using degradable polymer-lipid nanoparticles.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
James C
JC
Kaczmarek
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, NG7 2RD, UK.
Asha K
AK
Patel
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Kevin J
KJ
Kauffman
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Owen S
OS
Fenton
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Matthew J
MJ
Webber
Shire Pharmaceuticals, Lexington, MA, USA.
Michael W
MW
Heartlein
Shire Pharmaceuticals, Lexington, MA, USA.
Frank
F
DeRosa
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. dgander@mit.edu.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. dgander@mit.edu.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. dgander@mit.edu.|Harvard and MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA. dgander@mit.edu.
Daniel G
DG
Anderson
D061605:Administration, Intravenous; D000818:Animals; D008055:Lipids / Q000737:chemistry*; D008168:Lung / Q000737:chemistry*; D051379:Mice; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D012333:RNA, Messenger / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties
D008055:Lipids; D011108:Polymers; D012333:RNA, Messenger; C507253:poly(beta-amino ester)
PBAEs; drug delivery; mRNA; nanoparticles; serum stability
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