The Trojan Horse Liposome Technology for Nonviral Gene Transfer across the Blood-Brain Barrier

Figure 2

In vivo gene expression of a β-galactosidase reporter gene following systemic administration of THLs. (Top panels) β-galactoside histochemistry was performed on mouse brain and spleen removed 2 days after an IV injection of THLs carrying a β-galactosidase plasmid driven by either the SV40 promoter (SV40-lacZ-THL) (left panels) or Gfap promoter (Gfap-lacZ-THL) (right panels). THLs were targeted with the 8D3 antimouse TfRMAb. (Bottom panels) β-Galactosidase histochemistry of Rhesus monkey brain removed from either a monkey injected with THLs targeted with the HIRMAb ((a), (c), (d), (e), and (f)) or a control uninjected primate (b). The β-galactosidase expression plasmid is driven by the SV40 promoter. (a) shows a full coronal section of the primate forebrain. (c) shows half-coronal sections through the primate cerebrum and a full coronal section through the cerebellum; the sections from top to bottom are taken from the rostral to caudal parts of brain. (d, e, and f) are light micrographs of choroid plexus, occipital cortex, and cerebellum, respectively. All specimens are β-galactosidase histochemistry without counterstaining. The magnification in (a) and (b) is the same and the magnification bar in (a) is 3 mm; the magnification bar in (c) is 8 mm; the magnification bars in (d)–(f) are 155 μm. Top panels are from [21]. Bottom panels are from [34].