American Chemical Society
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Charge-Reversal Amphiphiles for Gene Delivery

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journal contribution
posted on 2004-10-06, 00:00 authored by Carla A. H. Prata, Yuxing Zhao, Philippe Barthelemy, Yougen Li, Dan Luo, Thomas J. McIntosh, Stephen J. Lee, Mark W. Grinstaff
Delivering a missing gene or a functional substitute of a defective gene has the potential to revolutionize current medical care. Of the two gene delivery approaches, viral and synthetic vectors, synthetic cationic vectors possess several practical advantages but suffer from poor transfection efficiency. A new approach to gene delivery using charge-reversal amphiphiles is described. This synthetic vector transforms from a cationic to an anionic amphiphile intracellularly. This amphiphile performs two roles:  first, it binds and then releases DNA, and second, as an anionic multicharged amphiphile, it destabilizes lipid bilayers. A charge-reversal amphiphile was synthesized and fully characterized, including the supramolecular complex it forms with DNA. Enhanced gene transfection was observed using these vectors compared to current cationic amphiphiles.

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