Post-Coded Ligands for Cell Sorting and Delivery

这里提出的工作的一般方法是，与其做一个单一的实验并得到一个单一的结果，为什么不同时进行10，000个实验并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10,000个分子，每个分子都带有一个邮政编码，不仅可以识别它们，还可以将它们送到特定的地址。将探索这种方法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是一个越来越重要的研究领域，基于细胞的治疗（例如用于移植的皮肤细胞的生长，基于干细胞的治疗，用于产生细胞衍生治疗的细胞的生长）或靶向体内的特定细胞或用于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。这里提出的是准备一个包含10，000个配体的文库，然后用细胞同时观察所有这些配体。将鉴定支持细胞生长并且是细胞友好的配体。那些被鉴定的配体将被附着在更大的玻璃表面上，并被研究以探索特异性和细胞选择性。另一个领域是细胞输送。通常很难将材料送入细胞，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10，000个分子，并研究所有这些分子如何与细胞一起工作，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）。那些被鉴定的分子将被详细地制备、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于所鉴定的细胞可渗透载体，从而允许多种化合物进入多种细胞。使用这些特洛伊木马，我们将向细胞中递送DNA样分子（反义分子），这些分子通常不会进入细胞，我们将使用它们来关闭基因。

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.