SIRNA NANOPARTICLES

SIRNA纳米粒子

• 批准号: 8168579
• 负责人: CYRUS R SAFINYA
• 金额: $ 0.65万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-15 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168579
• 关键词: Aminoglycosides; Behavior; Categories; Complex; Computer Retrieval of Information on Scientific Projects Database; Funding; Gene Silencing; Goals; Grant; Home environment; Image; Institution; Lipids; Nature; Phase; Research; Research Personnel; Resources; Roentgen Rays; Small Interfering RNA; Source; Structure; System; United States National Institutes of Health; nanoparticle; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Complexes comprising siRNA and lipidic aminoglycoside derivatives have been recently imaged by Cryo-EM, displaying a typical layered microstructure. In our lab we prepared lipid-siRNA constructs using a variety of lipid systems which have been successfully employed in gene silencing activities. The lipid-siRNA phase behavior appears to be very rich and so far we have identified by X-ray scattering three categories of supramolecular structures. Specifically: i) a lamellar phase obtained with commercially available cationic/non-ionic lipids, ii) a 2D hexagonal structure obtained with multivalent cationic lipids synthesized in our lab, and finally iii) a bicontinuous cubic phase obtained by a combination of a "cubic forming" neutral lipid and "home synthesized" multivalent cationic lipids (as well as commercially available). In addition, we have observed that the nature of the phase has a great impact on SE. We propose Cryo-EM experiments to obtain 2D images of the lipid nanoparticles alone and upon aggregation with siRNA. Our long-term goals are to locate the siRNA domains in the lipid-siRNA aggregate.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 复合物包含siRNA和拟南芥氨基糖苷衍生物最近已通过Cryo-EM成像，显示出典型的层状微观结构。 在我们的实验室中，我们使用各种脂质系统制备了脂质-siRNA构建体，这些脂质系统已成功地用于基因沉默活动。脂质-siRNA相行为似乎非常丰富，到目前为止，我们已经通过X射线散射确定了三类超分子结构。具体而言：i）用可商购的阳离子/非离子脂质获得的层状相，ii）用我们实验室合成的多价阳离子脂质获得的2D六边形结构，和最后iii）通过“形成立方体”的中性脂质和“自制的”多价阳离子脂质（以及可商购的）的组合获得的双连续立方体相。此外，我们还观察到，相位的性质对SE有很大的影响。 我们提出Cryo-EM实验来获得单独的脂质纳米颗粒和与siRNA聚集后的脂质纳米颗粒的2D图像。我们的长期目标是定位脂质-siRNA聚集体中的siRNA结构域。