Salvianolic acid B increases recombinant adeno-associated virus transduction through redirecting trafficking pathways and stabilizing perinuclear accumulations / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To screen small molecule compounds from traditional Chinese medicine that can enhance recombinant adeno-associated virus (rAAV) transduction. METHODS Recombinant adeno-associated virus (rAAV) has been established as a powerful tool for in vivo gene transfer and achieved much promise in gene therapy applications. However, widespread clinical use has been limited by transduction efficiency.In the current study,we screened a panel of small molecule compound from traditional Chinese medicine focused on AAV intracellular trafficking process and found salvianolic acid B can significantly enhance rAAV2 transduction. RESULTS Salvianolic acid B caused a dose-depen-dent increase in rAAV2 transduction regardless of vector dose,genome architecture,and over a broad range of cell line from various cell type and species(HEK293,HeLa,HepG2,Huh-7,CHO-K1,LO-2). Salvianolic acid B treatment redirected rAAV2 particles toward large vesicles positive for late endosomal (Rab7)and lysosomal(LAMP1)markers.Furthermore,salvianolic acid B acted to increase accumulation of viral particles at the perinuclear region. CONCLUSION In summary, our results suggest that salvi-anolic acid B redirects rAAV2 toward more productive trafficking pathways and stabilizes perinuclear accumulations of vectors,facilitating productive nuclear trafficking.