abstract |
The present invention provides a lentiviral vector comprising a codon optimized factor VIII sequence and methods of using such lentiviral vectors. The liver-targeted lentiviral vectors disclosed herein can be used in gene therapy, wherein the lentiviral gene delivery is a transgene expression cassette in a pediatric (e.g., newborn) or adult subject's targeted cells (e.g., hepatocytes). ) To stably integrate into the genome, thereby enhancing FVIII expression at low lentiviral vector doses (e.g., 5x10 10 TU/kg or less, such as 1.5x10 9 TU/kg or less or 1x10 8 TU/kg or less). Yes (for example, a 100x improvement) The present invention also provides a method of treating a bleeding disorder such as hemophilia (e.g., hemophilia A), wherein the method provides a low dose (1x10 8 TU/kg or less ~ 1.5x10 10 TU/kg) to a subject in need thereof. kg) a liver-targeting lentiviral vector comprising a codon-optimizing factor VIII nucleic acid sequence. |