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The gene transfection properties of a lipophosphoramidate derivative with two phytanyl chains

Paper ID Volume ID Publish Year Pages File Format Full-Text
6724 513 2012 14 PDF Available
Title
The gene transfection properties of a lipophosphoramidate derivative with two phytanyl chains
Abstract

Development of efficient and non-toxic gene delivery systems is among the most challenging requirements for successful gene therapy. Cationic lipophosphoramidates constitute a class of cationic lipids we have already shown to be efficient for in vivo gene transfer. Herein, we report the synthesis of a cationic lipophosphoramidate bearing two phytanyl chains (BSV18) as hydrophobic domain, and studied its gene transfection properties. In vitro, BSV18 exhibited a high transfection efficacy associated with a low cytotoxicity. 31P NMR studies of various cationic lipophosphoramidates in water solution suggested that the phytanyl chains may favor the formation of an inverted hexagonal phase, a supramolecular arrangement which is presumed to enhance the endosomal escape and consequently increase the transfection efficiency. In vivo, systemic delivery of BSV18-based lipoplexes allowed a high efficiency of gene transfection into the mouse lung. With a view to clinical application, we evaluated not only the efficiency of lung transfection but also the eventual in vivo side-effects. Thus, in addition to monitoring the in vivo transfection efficiency by bioluminescent imaging and identifying by immunohistochemistry the cell types transfected, we also assessed in living animals the potential liver reaction as well as the inflammatory and immune responses induced by BSV18-mediated transfection. All those adverse effects were actually highly transient. Thus, taken together, these results indicate that lipophosphoramidates equipped with two phytanyl chains may have great potential for lung gene therapy, in particular for Cystic Fibrosis.

Keywords
Cationic lipid; Lipophosphoramidate; Phytanyl chains; Transfection; Bioluminescence; Hepatotoxicity
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The gene transfection properties of a lipophosphoramidate derivative with two phytanyl chains
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 26, September 2012, Pages 6240–6253
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