Post-Coded Ligands for Cell Sorting and Delivery

这里提出的工作的一般方法是，与其做一个实验，得到一个结果，不如同时进行10,000个实验，从所有这些实验中获得高质量的数据。这种方法的关键是制造1万个分子，每个分子都带有邮政编码，这样不仅可以识别它们，还可以送到特定的地址。这种方法将被探索的一个领域是发现用于细胞结合的新配体。这是一个重要的研究领域，因为哺乳动物细胞的固定化是一个越来越重要的研究领域，基于细胞的治疗方法（例如用于移植的皮肤细胞的生长，基于干细胞的治疗方法，用于生产细胞源性治疗的细胞的生长）或针对体内特定细胞或基于细胞的纯化的显著增加。然而，在这一领域发现新的配体是困难和有限的。这里的建议是准备一个10000个配体的文库，然后与细胞同时观察所有这些配体。将确定支持细胞生长和对细胞友好的配体。这些被识别的配体将被附着在更大的玻璃表面，并被研究以探索特异性和细胞选择性。另一个领域是细胞传递。一般来说，将物质送入细胞是非常困难的，每种细胞类型在输送方面略有不同。在项目的这一部分，我们将构建10000个分子，观察它们在细胞中的行为，并检测那些最有效地进入细胞的分子（这将在许多不同的细胞类型中完成）。这些被识别的分子将被大量制备，并进行更详细的探索和检查。这些化合物将被用作特洛伊木马。在这种方法中，生物学上重要的分子将附着在鉴定的细胞渗透性载体上，从而允许各种化合物进入各种细胞。利用这些特洛伊木马，我们将把通常不会进入细胞的DNA分子（反义型分子）传递到细胞中，我们将用它们来关闭基因。

The general approach to the work proposed here is that rather than doing a single experiment and getting a single result why not carryout out 10,000 simultaneous experiments and obtain high quality data from all of these. The key to this approach is to make 10,000 molecules in such a way that each of them carries a postcode that allows them to not only be identified but also delivered to a specific address. One area where this approach will be explored is the discovery of new ligands for cell binding. This is an important area of research as the immobilization of mammalian cells is an increasingly important area of research, with the marked increase in cell based therapeutics (for example the growth of skin cells for grafting, to stem cells based therapies to the growth of cells for the production of cell-derived therapeutics) or the targeting of specific cells within the body or for cell-based purifications. However, the discovery of new ligands in this area is difficult and limited. What is proposed here is to prepare a library of 10,000 ligands and then to look at ALL these ligands simultaneously with cells. Ligands will be identified that support cell growth and that are cell-friendly . Those ligands that are identified will be attached to much larger glass surfaces and investigated to explore specificity and cell selectivity. Another area is in cell delivery. It is generally very difficult to get materials into cells and each cell type is slightly different in terms of delivery. In this part of the project we will build 10,000 molecules and look at how ALL of these behave with cells and detect those that enter into cells most efficiently (this will be done with a number of different cell types). Those molecules identified will be prepared en masse and explored and examined in much greater detail. These compounds will then be used as Trojan Horses. In this approach biologically important molecules will be attached to the identified cell permeable carriers thus allowing a variety of compounds to enter into a variety of cells. Using these Trojan Horses, we will deliver into cells DNA like molecules (antisense type molecules) that do not normally get into cells and which we will use to switch off genes.