Models for Cell Targeting
Our 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 (Table 1).
Table 1. Current Cell Targeting Models
| Cell Target | Disease/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, DCs, 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 Peyer’s patchs | increasing or ablating immune responses
genetic vaccines vs. HIV, influenza, and biodefense agents | - ideal administration sites: intradermal, intranasal, or oral
- near ideal pharmacology: cell targets generally directly accessible at innoculation 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)
|
