42. Differential Transduction Profiles of AAV Vectors in a Mouse Model of Human Glycosylation

Abstract

AAV Biologythe overexpression of ERI-1 determined an over 10-fold, selective reduction on ssAAV genome association with H3 and H4, while changes were negligible for scAAV DNA and for control cellular genes. Consistent with chromatin exerting a repressive role on ssAAV transduction, we also noticed that the downregulation of the main replication-dependent histone chaperone CAF-1 induced an over 20-fold increase in transduction. Increase of ssAAV2 transduction by ERI-1 also decreased the association, with the viral DNA, of proteins of the cellular DNA damage response (DDR; e.g. Nbs1 and Mre11), which our previous work had indicated as inhibitory of AAV transduction.Interestingly, DNA damage per se induced downregulation of histone gene expression. In particular, hydroxyurea, a drug markedly increasing AAV transduction, also determined histone mRNA degradation, an effect that required integrity of ERI-1.These results underline the importance of chromatin and its dynamic regulation in determining the fate of productive AAV transduction. These findings can be exploited for the development of more effective AAV-mediated gene delivery strategies.

Human-like NSG mouse glycoproteins sialylation pattern changes the phenotype of human lymphocytes and sensitivity to HIV-1 infection

“…Biodistribution and expression levels of recombinant adeno-associated virus (rAAV) vector delivered genes could be affected by sialylation of host receptors [5, 10, 44]. We compared the luciferase expression delivered by rAAV2/DJ8.…”

Human-like NSG mouse glycoproteins sialylation pattern changes the phenotype of human lymphocytes and sensitivity to HIV-1 infection

“…Biodistribution and expression levels of recombinant adeno-associated virus (rAAV) vector delivered genes could be affected by sialylation of host receptors [5, 10, 43]. We compared the luciferase expression delivered by rAAV2/DJ8.…”