LID-PEG Project 2 will develop sialoglycan-decorated nanoparticles to target siglecs on different inflammatory cells. Counter-receptor structural information will help generate enhanced siglec-targeting nanoparticles.
Siglecs are a family of immune receptors that bind sialic acid containing glycans as ligands. Most siglecs are expressed on leukocytes and are well documented as regulators of cell signaling in innate and adaptive immunity. The focus of this project is the development of nanoparticle platforms decorated with siglec ligands that are capable of selectively targeting and delivering cargo to cells expressing the corresponding siglec. In particular, the use of nanoparticles decorated with ligands to Siglec-8 (murine Siglec-F) to target eosinophils, Siglec-9 (murine Siglec-E) to target neutrophils, and sialoadhesin (Sn;Siglec-1) to target inflammatory monocytes/macrophages. Nanoparticles targeting each siglec will be used to investigate the roles of the corresponding cell types in disease processes, and to assess the utility of siglec-targeted nanoparticles in the diagnosis and treatment of lung disease.
This project will contribute to the innovation of the LID-PEG program through its development of siglec-ligand decorated nanoparticles capable of targeting and delivering cargo to leukocytes (eosinophils, neutrophils and monocytes/macrophages), and provide the LID-PEG team the tools for developing novel methods to detect and treat lung and cardiovascular disease processes. The successful demonstration of in vivo applications of this new class of nanoparticles, will contribute to utility of the entire class of non-antibody cell directed therapeutics.
Dr. James Paulson is a world leader in glycobiology, having pioneered many of the techniques that have accelerated discovery in the field for a generation. These include the chemo-enzymatic synthesis of glycans, which has enabled the production of sialoglycans and sialoglycan mimetics as tools for probing roles of sialic acids that will be invaluable to LID-PEG. His drug development experience (Cytel) adds translational research and management perspectives to this Program.
James C. Paulson
- Department of Chemical Physiology
The Scripps Research Institute
10550 North Torrey Pines Road
La Jolla, CA 92037
- Phone: 858-784-9634