Author : Nathan Francis Bouxsein
Publisher :
ISBN 13 : 9781124217680
Total Pages : 614 pages
Book Rating : 4.2/5 (176 download)
Book Synopsis The Structure-function Properties of Self-assembled Lipid-short Nucleic Acid Complexes by : Nathan Francis Bouxsein
Download or read book The Structure-function Properties of Self-assembled Lipid-short Nucleic Acid Complexes written by Nathan Francis Bouxsein and published by . This book was released on 2010 with total page 614 pages. Available in PDF, EPUB and Kindle. Book excerpt: We report on the gene silencing activities of Cationic Liposome (CL)-siRNA complexes transfected into cultured mammalian cells. We show that traditional CL formulations are inefficient delivery vectors for siRNA, requiring much larger CL:NA charge ratios for measurable activity. The high amount of CL required to achieve these charge ratios induces cellular toxicity, however, complex formulations with multivalent (5+) CLs can alleviate this effect. Additionally, we present new structural data suggesting that the internal organization of the siRNA within the complex is isotropic and not optimally packed. Poor packing negatively influences the stability of the complex and is related to the lower delivery efficiencies. Synchrotron x-ray diffraction experiments on model CL-short DNA complexes revealed that end stacking of the duplexes will promote a novel, highly ordered centered rectangular phase of DNA within the complex - in contrast to the unorganized siRNA. Furthermore, in systems designed to inhibit end stacking, the organization became dependent on the shape anisotropy of the NA, favoring longer sequences over shorter sequences. Taken together, we suggest some criteria for CL-short NA formulations that improve their overall stability and build towards more efficient CL-siRNA complexes for gene silencing.