Bulletin of the American Physical Society
2009 APS March Meeting
Volume 54, Number 1
Monday–Friday, March 16–20, 2009; Pittsburgh, Pennsylvania
Session Z3: Non-viral Based Gene Delivery Systems: Opportunities, Obstacles and Challenges |
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Sponsoring Units: DPOLY DBP Chair: Yongmei Wang, Memphis Room: 301/302 |
Friday, March 20, 2009 11:15AM - 11:51AM |
Z3.00001: Small Bioactive Lipoplex (SBL) Nanoparticles Self-Assembled at Elevated Temperature and Pressure Invited Speaker: Conventional lipoplex (cationic liposome/DNA complex) serves well for gene transfer in cultured cells. However, their \textit{in vivo} gene delivery activity is limited due to its relatively large size (\underline {$>$}100 nm). This is due to incomplete charge neutralization as a result of the steric hindrance during the complexation between DNA and liposomes. Behr et al hypothesized that monomolecular DNA condensate can be prepared if the DNA sees the cationic lipid as monomers. Indeed, small nanoparticles ($\sim $30 nm) were prepared by using a single-chain cationic amphiphile which has a high solubility at the physiological condition. To stabilize the monomolecular condensate, Behr has included a SH group in the cationic amphiphile which could be oxidized to form a dimer. Unfortunately, the stabilized nanoparticles showed no transfection activity when delivered into cells. We hypothesized that similar small lipoplex can be prepared by using a double-chain cationic amphiphile if both DNA and the amphiphile can be soluble in the same solvent. A hydrofluorocarbon HFC-152a is an excellent solvent for the cationic lipid DOTAP at an elevated temperature ($\sim $35 $^{\circ}$C) and pressure ($\sim $300 atm). Since the solvent can accommodate small amounts of water, DNA or siRNA could be introduced into the system to allow lipoplex formation. The resulting Small Bioactive Lipoplex (SBL) is 30-50 nm in diameter and can transfect cultured cells. Freeze-fracture electron microscopy showed that SBL are solid nanoparticles without any lipid bilayer structure. Since plasmid DNA is fragile at elevated temperature and pressure, we have concentrated our effort in siRNA which is stable under the same conditions. The new formulation shows great promise as an \textit{in vivo} delivery vector when small particles are required for efficient penetration into the tissues. [Preview Abstract] |
Friday, March 20, 2009 11:51AM - 12:27PM |
Z3.00002: New Developments in Non Viral Gene Delivery Invited Speaker: |
Friday, March 20, 2009 12:27PM - 1:03PM |
Z3.00003: Image-Guided Hydrodynamic Gene Delivery Invited Speaker: Gene delivery by rapid injection of a large volume of DNA solution into a blood vessel, commonly called hydrodynamic gene delivery, has become a common method for gene therapy studies in rodents. In this presentation, I will focus on our recent work aiming at establishment of an image-guided hydrodynamic procedure for gene delivery in humans. Our study employed swine as an animal model and the procedure developed includes image-guided insertion of a balloon catheter into the selected blood vessel of the targeted organ from the jugular vein and hydrodynamic injection of plasmid DNA in saline. The talk will cover the rationale of our approach, the effectiveness of procedure for gene delivery to liver and muscle, and the impact of the procedure on physiological functions and serum chemistry of the animals. The results will be discussed with respect to potential applications of the hydrodynamic gene delivery to human gene therapy. [Preview Abstract] |
Friday, March 20, 2009 1:03PM - 1:39PM |
Z3.00004: Revisit an old problem -- Complexation between DNA and PEI Invited Speaker: After revisiting the captioned problem by using a combination of chemical synthesis and physical methods, we studied the dynamics of the complexation between branched polyethyleneimine ($b$PEI) and plasmid DNA ($p$DNA) and characterized the structure, size and surface charge of the resultant DNA/PEI complexes (polyplexes). As expected, in order to reach a high efficiency in gene transfection into cells it is necessary to use a higher N:P ratio and make the polyplexes positively charged. Our results reveal that it is those uncomplexed $b$PEI chains free in the solution mixture that plays a vitally important role in enhancing the transfection efficiency, inspiring new thinking of how to correlate in vitro and in vivo studies so that we can improve the in vivo transfection efficiency. Increasing the N:P ratio normally results in a higher cytotoxicity, which is a catch-22 problem. Recently, we found that a proper modification of $b$PEI can greatly reduce its cytotoxicity without any suffering in the transfection efficiency. In this lecture, we will show that our properly modified $b$PEI is even much more effective and less cytotoxic in the gene transfection than those commercially available lipoflexes. Our recent breakthrough leads to a complete new direction in the development of non-viral vectors for molecular medicines, including gene transfection. [Preview Abstract] |
Friday, March 20, 2009 1:39PM - 2:15PM |
Z3.00005: Recent Developments in Non-Viral Gene Delivery Invited Speaker: |
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