Novel promoter, lentiviral vector and methods and uses thereof

Abstract

A promoter sequence comprising at least a portion of a ABCB4 promoter sequence (optionally human) or reverse complement thereof, wherein the splice sites of the ABCB4 promoter are mutated. A lentiviral vector sequence (optionally based on HIV) comprising the promoter sequence operably linked with a transgene, optionally wherein the promoter sequence and transgene are in reverse orientation to the transcription direction of the lentiviral vector sequence. The promoter or lentiviral vector sequence may further comprise an enhancer sequence. The transgene may encode a liver protein, liver transmembrane protein, ATB binding cassette transporter protein, ABCB4 (optionally human) or ABCB11. The lentiviral vector sequence may further comprise one or more miRNA sequences. A lentiviral vector comprising the lentiviral vector sequence. The lentiviral vector sequence or vector for use in therapy, optionally in the treatment of a liver disease, cholestasis, progressive familiar intrahepatic cholestasis (PFIC, optionally PFIC3), a disease or disorder associated with mutated and / or aberrant expression of ABCB4 (optionally intrahepatic cholestasis of pregnancy type 3, gallbladder disease 1, or low phospholipid associated cholelithiasis). Use of the promoter or lentivirus vector sequence to improve lentiviral titre. Related plasmids, host cells, compositions comprising a pharmaceutically acceptable carrier and sequences are disclosed. [Figure 1D]