Chemical & Biological Approaches for Cell Targeting

我们的总体目标是开发全面的技术，允许在体内进行小分子疗法、基因或蛋白质的细胞特异性传递。我们利用噬菌体展示文库来分离与特定细胞类型结合和入侵的多肽。这种方法适用于各种各样的细胞类型，我们已经为20种不同的细胞类型分离出了靶向肽。这些多肽表现出显著的细胞类型特异性。换句话说，与其他细胞类型相比，分离的多肽显示出对它们所选择的细胞类型的选择性，即使是那些密切相关的细胞类型。我们建议识别与免疫系统的关键细胞，即T细胞、B细胞和树突状细胞结合并介导细胞摄取的多肽。在体内靶向免疫细胞是医学上的一个主要挑战，在许多医学应用中，细胞特异性递送剂将是有利的。此外，免疫系统为我们提供了方便的生物输出，因此可以很容易地跟踪体内靶向的效果。随着靶向多肽的确定，它们将被用来在体外和体内将生物活性分子输送到细胞中。我们将在噬菌体的上下文中使用这些肽，并开发可用作所选噬菌体的替代品或与其结合使用的多肽支架。实现我们的目标将影响疫苗学和免疫调节疗法，以及解决体内细胞特异性递送领域的许多一般问题。

Our overall goal is to develop comprehensive technologies that allow for cell-specific delivery of small molecule therapeutics, genes, or proteins in vivo. We have employed phage display libraries to isolate peptides that bind to and invade specific cell types. This approach works with a wide variety of cell types and we have isolated targeting peptides for 20 different cell types. These peptides display remarkable cell- type specificity. In other words, the isolated peptides show selectivity for the cell type they were selected against in comparison to other cell types, even those that are closely related. We propose to identify peptides that bind to and mediate cellular uptake in to critical cells of the immune system, namely, T-cells, B-cells, and dendritic cells. Targeting immune cells in vivo represents a major challenge in medicine, and there are many medical applications in which cell-specific delivery agents would be advantageous. Furthermore, the immune system provides us with convenient biological outputs so that the effects of targeting in vivo can be easily followed. As targeting peptides are identified, they will be utilized to deliver biologically active molecules to the cells both in vitro and in vivo. We will use the peptides in the context of the phage as well as develop peptide scaffolds that can be used as replacements for or in conjunction with the selected phage. Achieving our goals will impact vaccinology and immunomodulation therapies as well as solving many general problems in the area of cell-specific delivery in vivo.