New strategies for nucleic acid delivery to conquer cellular and nuclear membranes.
After administration to the body, nucleic acid containing nanoparticles (NANs) need to cross several extra- and intracellular barriers to reach the cytoplasm or nucleus of the target cells. In the last decade several groups tried to overcome these barriers by arming non-viral delivery systems with targeting moieties, polyethylene glycol chains, fusogenic peptides and so forth. However, the drawback of this upgrading strategy is that each of the encountered barriers requires a new functionality, leading to very complex multi-component NANs. Moreover, there are currently no components available that can efficiently transport genes or NANs inside the nucleus of non-dividing cells. In this article a new, ultrasound based delivery system that possesses the capacity to simultaneously overcome several key barriers in non-viral nucleic acid delivery is presented. Additionally, a small amphiphilic compound that induces nuclear uptake of plasmid DNA and enhances non-viral gene transfer is presented.
Lentacker
Ine
I
Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
Vandenbroucke
Roosmarijn E
RE
Lucas
Bart
B
Demeester
Joseph
J
De Smedt
Stefaan C
SC
Sanders
Niek N
NN
D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D003511:Cyclohexanols / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D006801:Humans; D045423:Microbubbles; D053758:Nanoparticles; D009685:Nuclear Envelope / Q000378:metabolism*; D022022:Nuclear Pore / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000378:metabolism; D014162:Transfection / Q000379:methods*; D014465:Ultrasonics
D003511:Cyclohexanols; D010743:Phospholipids; D011092:Polyethylene Glycols; D004247:DNA; C064619:1,2-cyclohexanediol