Philip Leopold, Ph.D., professor and director of the department of chemistry, chemical biology, and biomedical engineering at the Stevens Institute of Technology, presented results of his group’s study of the packaging of DNA using rigid, polyunsaturated lipids.
This new class of cationic lipids was created at the Norwegian University of Science and Technology and Weill Cornell Medical College in Quatar, and has a structure related to carotenoids based on a linear, polyunsaturated chain with a second, shorter, saturated chain added on. The rigidity of the lipid would be predicted to interfere with packing of the DNA.
Indeed, the new lipids did bind DNA less tightly and offered less protection against degradation than a comparable cationic lipid, DC-Chol. However, in preliminary studies funded by the Qatar National Research Fund, it showed that its lipid provided a high transfection efficiency, most likely because loosely packaged DNA is easier to unpack in the cell.
Dr. Leopold believes this approach will translate well in vivo. “Most particles delivered in vivo are cleared from circulation by reticuloendothelial cells within minutes. Without taking extraordinary measures to avoid this fate, we are looking at a situation where particles will either hit their targets or miss on the first pass. Long-term stability of these particles in serum may be overrated as a parameter for evaluating synthetic gene transfer vectors. As long as the vectors keep their genetic payload together and deliver their cargo to target cells, less stability may be beneficial.”