Timed-release polymers as novel transfection reagents

Gillard, Marianne, Jia, Zhongfan, Gray, Peter P., Munro, Trent P. and Monteiro, Michael J. (2014) Timed-release polymers as novel transfection reagents. Polymer Chemistry, 5 10: 3372-3378. doi:10.1039/c4py00176a


Author Gillard, Marianne
Jia, Zhongfan
Gray, Peter P.
Munro, Trent P.
Monteiro, Michael J.
Title Timed-release polymers as novel transfection reagents
Journal name Polymer Chemistry   Check publisher's open access policy
ISSN 1759-9954
1759-9962
Publication date 2014-05-21
Year available 2014
Sub-type Article (original research)
DOI 10.1039/c4py00176a
Open Access Status Not Open Access
Volume 5
Issue 10
Start page 3372
End page 3378
Total pages 7
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Collection year 2015
Language eng
Subject 2507 Polymers and Plastics
1605 Policy and Administration
1303 Specialist Studies in Education
2204 Religion and Religious Studies
1502 Banking, Finance and Investment
Abstract Development of novel agents that mediate nucleic acid delivery into cells has widespread application from basic cell biology to gene therapy. Enabling subsequent gene expression relies on the efficient delivery of DNA into the nucleus. In this work, we have developed a series of polymers designed to release DNA, via a self-catalysed hydrolysis mechanism, in a time-dependent manner to test if release of DNA near the time of cell division (which typically occurs every 24 h in mammalian cells) would result in an increase in levels of gene expression. We utilize a transient gene expression system to test our delivery potential. Our results show that the polymers are able to bind to DNA for up to 24 h and in some cases 48 h before release, thus providing sufficient time for endosomal escape and transport to the nucleus. Polymer A-C3, which bound DNA for up to 48 h, was able to achieve the highest levels of transfection efficiency. Using a GFP reporter gene, up to 95% of cells were positive for gene expression, which was much greater than the commercially available Freestyle Max. This work demonstrates a link between protection of DNA against degradation and high levels of transfection, indicating that protection of DNA is also a limiting factor in successful transfection. We postulate that due to the strong binding of the polymers to the DNA and the large size of the polyplexes, which are significantly larger than the nuclear pores, entry into the nucleus occurs through passive transport during cell division and nuclear envelope breakdown. This journal is
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
 
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