Promoter CAG is more efficient than hepatocyte‑targeting TBG for transgene expression via rAAV8 in liver tissues.
Kang J, Hang L, Zheng W, Luo J, Zhang X, Song Y, Liu A.
Molecular medicine reports. 2022; 25(1):

Abstract

The recombinant adenoassociated virus 8 (rAAV8) vector is a widely used tool in basic research and clinical trials. The cytomegalovirus immediateearly enhancer/chicken betaactin (CAG) promoter is a synthetic promoter used in adenoviral constructs with a wide spectrum and notable efficiency. The thyroxine binding globulin (TBG) promoter is a liverspecific promoter, which directs transgene expression in hepatocytes. However, the transduction efficiency of the rAAV vector is dependent on both the administration routes and the promoter elements. In the present study, the transduction efficiency in the liver following intraperitoneal (IP) and intravenous (IV) injections of rAAV8 with the CAG, TBG669 and TBG410 promoters was compared. Enhanced green fluorescent protein (EGFP) expression was used as the biomarker to indicate efficiency. Among the three different promoters, CAG exhibited the highest efficiency from both IV and IP injections. Following IV administration, EGFP expression, induced by the CAG promoter, was 67fold higher compared with that in the TBG410 promoter group and 26fold higher compared with that in the TBG669 promoter group. EGFP protein expression was higher with IV injection compared with that for IP injection for both the CAG and TBG669 promoters (P<0.05). With the CAG promoter, EGFP protein expression was 1.5fold higher with the use of IV injection than with IP injection. With the TBG410 promoter, no differences were observed between the two administrations. In conclusion, these findings demonstrated that the CAG promoter was much more efficient at driving gene expression in the liver compared with that for the TBG promoters in rAAV8. In addition, IP administration produced comparable efficiency for gene delivery via the rAAV8 vector, particularly with the promoter TBG410.



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