shRNA Targeting Lentiviral Vector Minus-Strand Product Improves the Viral Titer During Viral Packaging.

Lentiviral vector (LVV) has been used as one of the common carriers for gene therapy in clinical trials. LVV-mediated clinical trials have being reported in successfully treating hundreds of β-thalassemia cases. These LVVs bear an inversely placed β-hemoglobin (HBB) gene expression cassette for preserving introns during the viral RNA packaging. Consequently, these LVVs often produce a small amount of negatively orientated transcript driven by its internal gene promoter and would lower the viral titer by the minus-strand complemented with the viral backbone. To overcome this problem, we designed shRNAs specifically target the minus-strand RNA driven by the LVV internal promoter that resulted in a notable increase in the viral titer. This report demonstrates a simple and positive mean for increasing the effectiveness for gene therapy with the LVV system.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)