基质刚性影响声孔效应介导的单细胞基因转染

实验研究了基质刚性对单细胞质粒DNA转染效果的影响。实验采用高声压短脉冲(0.45MPa,10μs)条件的超声对培养在不同硬度凝胶基质(软的凝胶基质：0.2kPa,硬的凝胶基质：40kPa)上的力学敏感细胞NIH 3T3进行质粒DNA转染实验。实验结果表明,培养在硬的凝胶基质上的细胞,质粒DNA转染效率明显高于培养在软的凝胶基质上的细胞。进一步对质粒DNA进行荧光示踪可知培养在不同刚性基质上的细胞导入质粒DNA的方式不同。当细胞被培养在硬的凝胶基质上时,通过声致穿孔产生的小孔进入细胞内的质粒DNA更多,而培养在软的凝胶基质上的细胞,更多的质粒DNA可以通过非声致穿孔作用,例如内吞方式导入细胞。 细胞骨架蛋白分布规律表明,硬的凝胶基质上培养的细胞内有更多的F肌动蛋白微丝,可以更好地支撑起细胞的铺展形态,相对不容易发生内吞作用。而软的凝胶基质上培养的细胞内F肌动蛋白则更多以球形状态存在,细胞形貌骗向圆形,此时更容易发生胞吞作用。     

Optimal vaccine scheduling in cancer immunotherapy

Cancer immunotherapy aims at stimulating the immune system to react against cancer stealth capabilities. It consists of repeatedly injecting small doses of a tumor-associated molecule one wants the immune system to recognize, until a consistent immune response directed against the tumor cells is observed.

We have applied the theory of optimal control to the problem of finding the optimal schedule of injections of an immunotherapeutic agent against cancer. The method employed works for a general ODE system and can be applied to find the optimal protocol in a variety of clinical problems where the kinetics of the drug or treatment and its influence on the normal physiologic functions have been described by a mathematical model.

We show that the choice of the cost function has dramatic effects on the kind of solution the optimization algorithm is able to find. This provides evidence that a careful ODE model and optimization schema must be designed by mathematicians and clinicians using their proper different perspectives.     

DNA体外缩合的研究进展

DNA缩合不仅是自然界常见的生理现象，也是非病毒载体介导基因转染的关键步骤。了解DNA体外缩合的性质与特征，将有助于设计出高效的非病毒转基因载体。本文综述了近十几年来以多价阳离子为缩合剂诱发的DNA体外缩合的研究进展，着重介绍了缩合的机理、过程、影响缩合的因素以及应用于转基因的最新成果。     

赖氨酸修饰壳聚糖磁性超微载体的制备和表征

本文设计并合成了良好水溶性的赖氨酸修饰壳聚糖,并对制备工艺进行了优化.产物通过红外(FTIR)和核磁(1H-NMR)进行了表征,并将其作为壳层材料制备了赖氨酸修饰壳聚糖磁性超微载体.通过光电能谱(XPS)、透射(TEM)、激光粒度仪、X射线衍射(XRD)、磁性能测试(VSM)对载体进行了表征.结果表明,制备的赖氨酸修饰壳聚糖磁性超微载体表面带有大量的氨基(-NH2),粒径分布较为均一(100nm左右),形貌较为规则,并具有良好的超顺磁性,因而该载体具有更加良好的性能.     

A combination of modified particle swarm optimization algorithm and support vector machine for gene selection and tumor classification

In the analysis of gene expression profiles, the number of tissue samples with genes expression levels available is usually small compared with the number of genes. This can lead either to possible overfitting or even to a complete failure in analysis of microarray data. The selection of genes that are really indicative of the tissue classification concerned is becoming one of the key steps in microarray studies. In the present paper, we have combined the modified discrete particle swarm optimization (PSO) and support vector machines (SVM) for tumor classification. The modified discrete PSO is applied to select genes, while SVM is used as the classifier or the evaluator. The proposed approach is used to the microarray data of 22 normal and 40 colon tumor tissues and showed good prediction performance. It has been demonstrated that the modified PSO is a useful tool for gene selection and mining high dimension data.     

Chromatography of plasmid DNA

Liquid chromatography plays a central role in process-scale manufacturing of therapeutic plasmid DNA (pDNA) for gene therapy and DNA vaccination. Apart from its use as a preparative purification step, it is also very useful as an analytical tool to monitor and control pDNA quality during processing and in final formulations. This paper gives an overview of the use of pDNA chromatography. The specificity of pDNA purification and the consequent limitations to the performance of chromatography are described. Strategies currently used to overcome those limitations, as well as other possible solutions are presented. Applications of the different types of chromatography to the purification of therapeutic pDNA are reviewed, and the main advantages and disadvantages behind each technique highlighted.     

Fluorescence-based nucleic acid detection and microarrays

Recent analytical innovations for nucleic acid detection have revolutionized the biological sciences. Single nucleic acid sequence detection methods have been expanded to incorporate multiplexed detection strategies. A variety of nucleic acid detection formats are now available that can address high throughput genomic interrogation. Many of these parallel detection platforms or arrays, employ fluorescence as the signaling method. Fluorescence-based assays offer many advantages, including increased sensitivity, safety and multiplexing capabilities, as well as the ability to measure multiple fluorescence properties. Multiplexed microarray platforms provide parallel detection capabilities capable of measuring thousands of simultaneous responses. This review will discuss both single target detection and microarray applications with a focus on gene expression and pathogenic microorganism (PM) detection.     

基于碳水化合物的阳离子聚合物载体在基因释放中的应用

在基因治疗中,基因释放载体是不可缺少的重要组成部分.近几年来聚合物基因释放载体的研究主要旨在开发低毒或无毒的阳离子聚合物用于安全有效的基因释放.作为一类天然化合物,基于碳水化合物的阳离子聚合物载体由于其良好的生物相容性和低毒性被广泛地研究并应用于基因释放.本文阐述了聚合物基因释放的机理,并对近几年来一些典型的含碳水化合物的阳离子聚合物基因释放载体作一综述.