One size does not fit all: The effect of chain length and charge density of poly(ethylene imine) based copolymers on delivery of pDNA, mRNA, and repRNA polyplexes.

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Title: One size does not fit all: The effect of chain length and charge density of poly(ethylene imine) based copolymers on delivery of pDNA, mRNA, and repRNA polyplexes.
Authors: Blakney, AK
Yilmaz, G
McKay, PF
Becer, CR
Shattock, RJ
Item Type: Journal Article
Abstract: Nucleic acid delivery systems are commonly translated between different modalities, such as DNA and RNA of varying length and structure, despite physical differences in these molecules that yield disparate delivery efficiency with the same system. Here, we synthesized a library of poly(2-ethyl-2-oxazoline)/poly(ethylene imine) copolymers with varying molar mass and charge densities in order to probe how pDNA, mRNA, and RepRNA polyplex characteristics affect transfection efficiency. The library was utilized in a full factorial design of experiment (DoE) screening, with outputs of luciferase expression, particle size, surface charge, and particle concentration. The optimal copolymer molar mass and charge density was found as 83 kDa/100%, 72 kDa/100%, and 45 kDa/80% for pDNA, RepRNA, and mRNA, respectively. While 10 of the synthesized copolymers enhanced the transfection efficiency of pDNA and mRNA, only 2 copolymers enhanced RepRNA transfection efficiency, indicating a narrow and more stringent design space for RepRNA. These findings suggest that there is not a "one size fits all" polymer for different nucleic acid species.
Issue Date: 26-Apr-2018
Date of Acceptance: 24-Apr-2018
URI: http://hdl.handle.net/10044/1/59807
DOI: https://doi.org/10.1021/acs.biomac.8b00429
ISSN: 1525-7797
Publisher: American Chemical Society
Start Page: 2870
End Page: 2879
Journal / Book Title: Biomacromolecules
Volume: 19
Issue: 7
Copyright Statement: © 2018 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomacromolecules, after peer review and technical editing by the publisher. To access the final edited and published work see https://dx.doi.org/10.1021/acs.biomac.8b00429
Sponsor/Funder: Medical Research Council (MRC)
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: MC_PC15028
EP/R013764/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biochemistry & Molecular Biology
Chemistry, Organic
Polymer Science
Chemistry
RING-OPENING POLYMERIZATION
NONVIRAL GENE DELIVERY
CELLULAR UPTAKE
SIRNA DELIVERY
PLASMID DNA
IN-VITRO
VACCINES
POLY(2-ETHYL-2-OXAZOLINE)
POLYETHYLENIMINE
TRANSFECTION
HEK293 Cells
Humans
Oxazoles
Plasmids
Polyethyleneimine
RNA, Messenger
RNA, Small Interfering
Static Electricity
Surface-Active Agents
Transfection
Humans
Polyethyleneimine
Oxazoles
RNA, Small Interfering
RNA, Messenger
Surface-Active Agents
Transfection
Plasmids
Static Electricity
HEK293 Cells
Polymers
03 Chemical Sciences
06 Biological Sciences
09 Engineering
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-04-26
Appears in Collections:Department of Medicine
Faculty of Medicine



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