A Polyethylenimine-Linoleic Acid Conjugate for Antisense Oligonucleotide Delivery
Joint Authors
Xie, Jing
Yang, Zhaogang
Zhou, Chenguang
Liu, Yang
Yung, Bryant C.
Lee, Robert J.
Teng, Lesheng
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-06-01
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
A novel antisense oligonucleotide (ASO) carrier, polyethylenimine conjugated to linoleic acid (PEI-LA), was synthesized and evaluated for delivery of LOR-2501 to tumor cells.
LOR-2501 is an ASO targeting ribonucleotide reductase R1 subunit (RRM1).
In this study, PEI-LA was synthesized by reacting PEI (Mw ~ 800) with linoleoyl chloride.
Gel retardation assay showed complete complexation between PEI-LA and LOR-2501 at N/P ratio above 8.
No significant cytotoxicity was observed with these complexes at the tested dosage levels.
Interestingly, at N/P ratio of >6, levels of cellular uptake of PEI-LA/LOR-2501 were double that of PEI/LOR-2501 complexes of the same N/P ratio.
PEI-LA/LOR-2501 induced downregulation of 64% and 70% of RRM1 at mRNA and protein levels, respectively.
The highest transfection activity was shown by PEI-LA/LOR-2501 complexes at N/P ratio of 10.
Finally, using pathway specific inhibitors, clathrin-mediated endocytosis was shown to be the principle mechanism of cellular internalization of these complexes.
In conclusion, PEI-LA is a promising agent for the delivery of ASOs and warrants further investigation.
American Psychological Association (APA)
Xie, Jing& Teng, Lesheng& Yang, Zhaogang& Zhou, Chenguang& Liu, Yang& Yung, Bryant C.…[et al.]. 2013. A Polyethylenimine-Linoleic Acid Conjugate for Antisense Oligonucleotide Delivery. BioMed Research International،Vol. 2013, no. 2013, pp.1-7.
https://search.emarefa.net/detail/BIM-1030824
Modern Language Association (MLA)
Xie, Jing…[et al.]. A Polyethylenimine-Linoleic Acid Conjugate for Antisense Oligonucleotide Delivery. BioMed Research International No. 2013 (2013), pp.1-7.
https://search.emarefa.net/detail/BIM-1030824
American Medical Association (AMA)
Xie, Jing& Teng, Lesheng& Yang, Zhaogang& Zhou, Chenguang& Liu, Yang& Yung, Bryant C.…[et al.]. A Polyethylenimine-Linoleic Acid Conjugate for Antisense Oligonucleotide Delivery. BioMed Research International. 2013. Vol. 2013, no. 2013, pp.1-7.
https://search.emarefa.net/detail/BIM-1030824
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1030824