Chemical & Biological Approaches for Cell Targeting

我们的总体目标是开发全面的技术，允许在体内细胞特异性递送小分子治疗剂，基因或蛋白质。 我们已经采用噬菌体展示文库来分离结合并侵入特定细胞类型的肽。 这种方法适用于多种细胞类型，我们已经分离出20种不同细胞类型的靶向肽。 这些肽显示出显著的细胞类型特异性。 换句话说，与其他细胞类型相比，分离的肽显示出对它们所选择的细胞类型的选择性，即使是密切相关的那些。 我们建议鉴定结合并介导细胞摄取到免疫系统的关键细胞，即T细胞，B细胞和树突状细胞的肽。 体内靶向免疫细胞代表了医学中的主要挑战，并且存在许多其中细胞特异性递送剂将是有利的医学应用。 此外，免疫系统为我们提供了方便的生物输出，以便可以容易地跟踪体内靶向的效果。 当靶向肽被鉴定时，它们将被用于在体外和体内将生物活性分子递送至细胞。 我们将在噬菌体的背景下使用肽，以及开发肽支架，其可以用作所选噬菌体的替代物或与所选噬菌体结合。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.