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

  1. need for systemic distribution , but muscle-targeted delivery
  2. absence of cell-specific ligands
  3. multiple tissue barriers between blood and target cells

breast cancer

Breast Cancer

  1. need for systemic distribution , but cancer-targeted delivery
  2. target primary and metastatic sites
  3. absence of cell-specific ligands
  4. multiple tissue barriers between blood and target cells

B cell cancer

Chronic Lymphocytic Leukemia (CLL)

  1. need for systemic distribution , but cancer-targeted delivery
  2. absence of cell-specific ligands
  3. ideal pharmacology, few formal tissue barriers, cells in blood and marrow
  4. CLL cells poorly uptake vectors

myelogenous cancer

Chronic Myelogenous Leukemia (CML)

  1. need for systemic distribution , but cancer-targeted delivery
  2. absence of cell-specific ligands
  3. near ideal pharmacology, few formal tissue barriers, cells in blood and marrow

liver

Propionic Acidemia

  1. vector already goes to liver, need to detarget its delivery to Kupffer cells, DCs, and endothelial cells
  2. few useful cell-specific ligands
  3. 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

  1. ideal administration sites: intradermal, intranasal, or oral
  2. near ideal pharmacology: cell targets generally directly accessible at innoculation site
  3. absence of cell-specific ligands
  4. for oral delivery, need to avoid low pH of stomach and proteases of the gut (use enteric-coated capsules)