High‐level expression of naked DNA delivered to rat liver via tail vein injection

Abstract

These results demonstrate that gene transfer into the liver via rapid tail vein injection can easily be achieved in the rat, which is more than 10 times larger than the mouse, and has significant value for gene function analysis in rats.

Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar–Kyoto rats

“…Similar to the results in our previous study using pCAGGS-lacZ, 22 vIL-10 gene expression after pCAGGSvIL-10 injection was seen in the hepatocytes. Compared with the result in our previous study, the present study demonstrated a lower percentage of vIL-10-transfected cells.…”

“…As in previous reports, 20,22 we noted that transgenederived vIL-10 mRNA could also be detected in the kidney by quantitative real-time PCR. Plasmid DNA can also be delivered to the kidney via the retrograde renal vein route.…”

“…Nonetheless, we recently showed that this technique is also useful for gene transfer in normal rats, using pCAGGS-Epo. 22 We obtained maximal Epo expression when the DNA solution was rapidly injected in a volume of approximately 100 ml/kg body weight. The peak serum Epo levels following the tail vein injection of 800 mg of pCAGGS-Epo were 100-fold greater than the levels reached following the muscle-targeted gene transfer of 400 mg of pCAGGS-Epo by in vivo electroporation.…”

“…Plasmid DNA can also be delivered to the kidney via the retrograde renal vein route. 20,22 Therefore, we needed to take vIL-10 expression in the kidney into account in assessing the favorable effects of gene transfer via tail vein injection on the crescentic GN in WKY rats. Recently, we developed a technique for kidney-targeted plasmid DNA transfer in vIL-10 gene transfer in a glomerulonephritis model N Higuchi et al rats by retrograde renal vein injection.…”

“…20,21 We demonstrated that this technique is also useful for the delivery of a therapeutic protein into normal rats, using a rat erythropoietin (Epo) expression plasmid vector pCAGGS-Epo. 22 Here we tested the effectiveness of vIL-10 gene transfer by hydrodynamics-based transfection for the suppression of crescentic GN in WKY rats. We used the vIL-10 expression plasmid vector pCAGGSvIL-10, which drives vIL-10 cDNA expression under the CAG (cytomegalovirus immediate-early enhancer/ chicken b-actin hybrid) promoter.…”