Specific expression in brain of exogenous gene by transpassing blood-brain barrier after intravenous injection

Abstract

To study the expression of exogenous LacZ gene in brain via a delivery of OX26-pGFAP-IL. pCMV-Liposome, OX26-pCMV-IL, OX26-pGFAP-IL and blank liposome were injected into rats via femoral vein. At 24 h post-injection, the method of Q-PCR was adopted to calculate the relative quantities of LacZ gene mRNA in brain and peripheral organs. At 48 h post-injection, the protein expression of LacZ gene was detected by the activity of beta-galactosidase and the method of histochemical stain. The result of Q-PCR showed that, at 24 h post-injection, the relative quantities of LacZ mRNA in OX26-pCMV-IL group (49.2 x 10(-6)) and OX26-pGFAP-IL group (44.9 x 10(-6)) were significantly higher than pCMV-liposome and blank liposome groups (P < 0.05). In peripheral organs, the relative quantity of LacZ mRNA in OX26-pCMV-IL group were significantly higher than that in OX26-pGFAP-IL group (P < 0.05). At 48 h post-injection, the activity of beta-galactosidase in OX26-pCMV-IL (0.67 pg/mg) and OX26-pGFAP-IL groups (0.92 pg/mg) were significantly higher than pCMV-liposome and blank liposome groups (P < 0.05). There was no significant difference between OX26-pCMV-IL group and OX26-pGFAP-IL group in terms of the expression of beta-galactosidase. The result of histochemical stain showed that OX26-pGFAP-IL achieved a specifically positive expression in brain and had a decreased expression in peripheral organs. OX26-pGFAP-IL injected via femoral vein can cross the brain-blood barrier and achieve a specific expression in brain under the control of GFAP promoter. OX26-pGFAP-IL decreases the non-specific expression in peripheral organs and it may be used as an non-viral gene therapy for intra-cranial diseases.