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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI050235-03
Application #
6750037
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Gondre-Lewis, Timothy A
Project Start
2002-06-15
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2006-05-31
Support Year
3
Fiscal Year
2004
Total Cost
$390,000
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
McGuire, Michael J; Samli, Kausar N; Chang, Ya-Ching et al. (2006) Novel ligands for cancer diagnosis: selection of peptide ligands for identification and isolation of B-cell lymphomas. Exp Hematol 34:443-52
McGuire, Michael J; Sykes, Kathryn F; Samli, Kausar N et al. (2004) A library-selected, Langerhans cell-targeting peptide enhances an immune response. DNA Cell Biol 23:742-52