Use of lentiviral vectors expressing factor VIII

The present disclosure provides lentiviral vectors comprising codon optimized Factor VIII sequences, and methods of using such lentiviral vectors. The liver-targeted lentiviral vectors disclosed herein can be used for gene therapy, wherein the lentiviral gene delivery enables stable integration of t...

Full description

Saved in:
Bibliographic Details
Main Authors CANTORE, ALESSIO, NALDINI, LUIGI, PETERS, ROBERT T, ANNONI, ANDREA, PATARROYO-WHITE, SUSANNAH, MOFFIT, JEFF, MILANI, MICHELA, LIU, TONGYAO, SEREGIN, ALEXEY, DRAGER, DOUGLAS
Format Patent
LanguageChinese
English
Published 16.12.2019
Subjects
BEER
BIOCHEMISTRY
CHEMISTRY
COMPOSITIONS THEREOF
CULTURE MEDIA
DERIVATIVES THEREOF
ENZYMOLOGY
METALLURGY
MICROBIOLOGY
MICROORGANISMS OR ENZYMES
MUTATION OR GENETIC ENGINEERING
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC CHEMISTRY
PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS
SPIRITS
SUGARS
VINEGAR
WINE
Online AccessGet full text

Cover

More Information
Summary:The present disclosure provides lentiviral vectors comprising codon optimized Factor VIII sequences, and methods of using such lentiviral vectors. The liver-targeted lentiviral vectors disclosed herein can be used for gene therapy, wherein the lentiviral gene delivery enables stable integration of the transgene expression cassette into the genome of targeted cells (e.g., hepatocytes) of pediatric (e.g., neonatal) or adult subjects, achieving an improvement in FVIII expression (for example, a 100-fold improvement) at low lentiviral vector doses (e.g., 5*1010 or lower, such as 1.5*109 or lower, or 1*108TU/kg or lower). The present disclosure also provides methods of treating bleeding disorders such as hemophilia (e.g., hemophilia A) comprising administering to a subject in need thereof a liver-targeted lentiviral vector comprising a codon optimized Factor VIII nucleic acid sequence at low dosages (1*108 TU/kg or lower to 1.5*1010TU/kg).
Bibliography:Application Number: TW20198103837