Vascular endothelial growth factor broadens lentivector distribution in the heart after neonatal injection.
For some applications, the success of gene therapy depends on the efficiency of gene transfer into target organs, however, delivery to many tissues is limited. Efforts have been made to improve the efficiency of gene transfer into target organs such as the brain by using mannitol or vascular endothelial growth factor (VEGF) prior to gene delivery, since these treatments have been reported to increase vascular permeability in experimental animals. Here, we investigated the effect of VEGF pretreatment of neonatal mice on the ability of injected lentivirus (LV)--engineering expression of firefly luciferase (luc)--to enhance the transduction of various organs, including the brain and heart. LV/luc was delivered to VEGF-treated neonatal mice via the temporal vein. Whole-body bioluminescence imaging (WBLI) of luciferase expression showed that VEGF pretreatment does not diminish transgene expression over time since it remained steady for up to 12 weeks. Ex vivo imaging of the organs and assessments of organ luciferase activity showed that VEGF pretreatment resulted in significantly increased luciferase expression not only in the heart, but also in the brain, lung, and kidney. This study shows that VEGF may have therapeutic importance to enhance the efficiency of viral gene delivery to the heart, as well as to other target organs.
Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. tksato@mail.tains.tohoku.ac.jp
Takeya
T
Sato
Shobha
S
Ramsubir
Koji
K
Higuchi
Teruyuki
T
Yanagisawa
Jeffrey A
JA
Medin
D000818:Animals; D000831:Animals, Newborn; D015870:Gene Expression / Q000187:drug effects*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D016086:Lentivirus / Q000235:genetics*; D049409:Luciferases, Firefly / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000201:enzymology*; D013268:Stimulation, Chemical; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology*
D042461:Vascular Endothelial Growth Factor A; D049409:Luciferases, Firefly