Models for Cell Targeting

The Virology, Vector and Vaccine Engineering Laboratory's current ligand and vector targeting efforts are directed against several cell targets. Each target system has been selected for its distinct biology and differing pharmacological hurdles.

Current cell targeting models

Cell target	Disease or application	Pharmacologic issues
Skeletal muscle	Muscular dystrophy	Need for systemic distribution, but muscle-targeted delivery Absence of cell-specific ligands Multiple tissue barriers between blood and target cells
Breast cancer	Breast cancer	Need for systemic distribution, but cancer-targeted delivery Target primary and metastatic sites Absence of cell-specific ligands Multiple tissue barriers between blood and target cells
B cell cancer	Chronic lymphocytic leukemia (CLL)	Need for systemic distribution, but cancer-targeted delivery Absence of cell-specific ligands Ideal pharmacology, few formal tissue barriers, cells in blood and marrow CLL cells poorly uptake vectors
Myelogenous cancer	Chronic myelogenous leukemia (CML)	Need for systemic distribution, but cancer-targeted delivery Absence of cell-specific ligands Near ideal pharmacology, few formal tissue barriers, cells in blood and marrow
Liver	Propionic acidemia	Vector already goes to liver — need to detarget its delivery to Kupffer cells, dendritic cells and endothelial cells Few useful cell-specific ligands Ideal pharmacology, no tissue barriers, large fenestrations from blood into target site
Dendritic cells (DCs), mucosal M cells and Peyer's patches	Increasing or ablating immune responses; genetic vaccines versus HIV, influenza and biodefense agents	Ideal administration sites: intradermal, intranasal or oral Nearly ideal pharmacology: cell targets generally directly accessible at inoculation site Absence of cell-specific ligands For oral delivery, need to avoid low pH of stomach and proteases of the gut (use enteric-coated capsules)