The Trojan Horse Liposome Technology for Nonviral Gene Transfer across the Blood-Brain Barrier
Figure 5
Enzyme replacement therapy in a Parkinson’s disease model using THLs and TH genomic expression vectors. (a) Diagrams of four rat TH expression plasmids. The poly(A) transcription termination sequence is the SV40 3′-untranslated region (UTR) derived from the pGL2 promoter vector (Promega) for both clone 877 and prgTH4, whereas the poly(A) signal for prgTH2 and prgTH3 is derived from the rat TH gene. (b) Striatal TH enzyme activity on the side ipsilateral to the toxin lesion at 3, 6, and 10 days after a single injection of either saline or THLs carrying clone 877 alone, prgTH3 alone, or clone 877 + prgTH3 combined. Data are mean ± S.E. ( = 3–6 rats per point), and statistically significant differences were determined by Student’s -test. All plasmids were delivered to rat brain following the intravenous injection of TfRMAb-targeted THLs. The TH activity at 3 days following combination therapy is significantly greater than prgTH3 alone at 3 and 6 days after injection () and is greater than clone 877 alone at 10 days after injection (). (c) Apomorphine-induced rotations at 3, 6, and 10 days after a single injection of either saline or THLs carrying clone 877 alone, prgTH3 alone, or clone 877 + prgTH3 combined. Data are mean ± S.E. (–6 rats per point). The rotation behavior at 3 days following combination therapy is significantly reduced as compared to prgTH3 alone at 3 days after injection () and is significantly reduced as compared to clone 877 alone at 10 days after injection (). From [48].
