Post-Coded Ligands for Cell Sorting and Delivery

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.