Optimization of a Degradable Polymer–Lipid
Nanoparticle for Potent Systemic Delivery of mRNA to the Lung Endothelium
and Immune Cells
Version 2 2018-09-20, 18:19
Version 1 2018-09-20, 18:18
Posted on 2018-09-20 - 18:19
mRNA
therapeutics hold great potential for treating a variety of diseases
through protein-replacement, immunomodulation, and gene editing. However,
much like siRNA therapy the majority of progress in mRNA delivery
has been confined to the liver. Previously, we demonstrated that poly(β-amino
esters), a class of degradable polymers, are capable of systemic mRNA
delivery to the lungs in mice when formulated into nanoparticles with
poly(ethylene glycol)–lipid conjugates. Using experimental
design, a statistical approach to optimization that reduces experimental
burden, we demonstrate herein that these degradable polymer–lipid
nanoparticles can be optimized in terms of polymer synthesis and nanoparticle
formulation to achieve a multiple order-of-magnitude increase in potency.
Furthermore, using genetically engineered Cre reporter mice, we demonstrate
that mRNA is functionally delivered to both the lung endothelium and
pulmonary immune cells, expanding the potential utility of these nanoparticles.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Kaczmarek, James C.; Kauffman, Kevin J.; Fenton, Owen S.; Sadtler, Kaitlyn; Patel, Asha K.; Heartlein, Michael W.; et al. (2018). Optimization of a Degradable Polymer–Lipid
Nanoparticle for Potent Systemic Delivery of mRNA to the Lung Endothelium
and Immune Cells. ACS Publications. Collection. https://doi.org/10.1021/acs.nanolett.8b02917
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (8)
JK
James C. Kaczmarek
KK
Kevin J. Kauffman
OF
Owen S. Fenton
KS
Kaitlyn Sadtler
AP
Asha K. Patel
MH
Michael W. Heartlein
FD
Frank DeRosa
DA
Daniel G. Anderson