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Reconfiguring polylysine architectures for controlling polyplex binding and non-viral transfection

Paper ID Volume ID Publish Year Pages File Format Full-Text
7432 552 2011 13 PDF Available
Title
Reconfiguring polylysine architectures for controlling polyplex binding and non-viral transfection
Abstract

Poly(l-lysine) (PLL) is a cationic polyelectrolyte of interest for many applications, including in therapeutic biology for DNA complexation and transfection. Several non-lysine based polycations have been shown to afford more efficient transfection in live cells than has been achieved with PLL. We find that reconfiguring polylysine into short oligolysine grafts, strung from a hydrophobic polymer backbone, gives transfection reagents greatly superior to PLL, despite having the identical cationic functional groups (i.e., exclusively primary amines). Altering the oligolysine graft length modulates DNA-polymer interactions and transfection efficiency, while incorporating the PKKKRKV heptapeptide (the Simian virus SV40 large T-antigen nuclear localization sequence) pendent groups onto the polymer backbone led to even greater transfection efficiency over the oligolysine-grafted structures. Protein expression levels obtained with these novel polymer transfection reagents were higher than, or comparable to, expression seen in the cases of JetPEI™, FuGENE® 6 and Lipofectamine™ 2000, the later being notorious for cytotoxicity that accompanies high transfection efficiency. The relative strength of the polymer-DNA complex is key to the transfection performance, as judged by serum stability and PicoGreen analysis. Moreover, polyplexes formed from our graft copolymer structures exhibit low cytotoxicity, contributing to the therapeutic promise of these novel reagents.

Keywords
Gene therapy; Ring-opening metathesis polymerization (ROMP); Poly(cyclooctene-g-oligopeptide); Nuclear localization signal (NLS); Polylysine (PLL)
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Reconfiguring polylysine architectures for controlling polyplex binding and non-viral transfection
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 9, March 2011, Pages 2432–2444
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us