Polymer-lipid nanoparticles for systemic delivery of mRNA to the lungs
File(s)nihms-841031.pdf (688.98 KB)
Accepted version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2016-10-24
Date Acceptance
2016-09-30
Citation
Angewandte Chemie International Edition, 2016, 55 (44), pp.13808-13812
ISSN
1521-3757
Publisher
Wiley
Start Page
13808
End Page
13812
Journal / Book Title
Angewandte Chemie International Edition
Volume
55
Issue
44
Copyright Statement
© 2016 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer reviewed version of the following article which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201608450. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000387024200025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
drug delivery
mRNA
nanoparticles
PBAEs
serum stability
GENE DELIVERY
IN-VIVO
POLY(BETA-AMINO ESTER)S
CELLULAR UPTAKE
DNA DELIVERY
THERAPEUTICS
OPTIMIZATION
THERAPY
CELLS
Publication Status
Published
Date Publish Online
2016-09-30