Oxford Biomedica (uk) Limited

The University of North Carolina at Chapel Hill

Oxford Biomedia (uk) Limited

Jonathan Rohll

Alan John Kingsman

Kyriacos Andreou Mitrophanous

Miles William Carroll

Fiona Margaret Ellard

Susan Marie Kingsman

Narry Kim

John Christian Olsen

James Miskin

Nicholas D Mazarakis

Enca Martin-Rendon

Mimoun Azzouz

Kyri Mitrophanous

The present invention provides a vector system comprising a mutated post-transcriptional regulatory element. In particular, the present invention relates to a mutated WPRE sequence that can efficiently express nucleotides of interest in a retroviral vector system. The present invention also relates to methods of delivering and expressing nucleotides of interest to a target cell.

Vector system

Provided are retroviral vector genomes and vector systems comprising the genomes. In particular, a retroviral vector genome comprising two or more NOIs, operably linked by one or more Internal Ribosome Entry Site(s); a lentiviral vector genome comprising two or more NOIs suitable for treating a neurodegenerative disorder; and a lentiviral vector genome which encodes tyrosine hydroxylase, GTP-cyclohydrolase I and, optionally, Aromatic Amino Acid Dopa Decarboxylase are provided.

A method for producing viral vectors is described using packaging and producer cell lines is described. The producer cell comprises: (i) a first nucleotide sequence (NS) encoding a toxic viral envelope protein operably linked to a promoter; wherein the promoter is operably linked to at least one copy of a TRE; (ii) a second NS wherein the second NS comprises a sequence encoding a tetracycline modulator; (iii) a third NS encoding a retrovirus nucleocapsid protein; and (iv) a fourth NS comprising a retroviral sequence capable of being encapsidated in the nucleocapsid protein such that the retroviral vector particle titre obtainable from the producer cell is regulatable by tetracycline and an initial stimulus with sodium butyrate or functional analogues thereof.

Methods for producing high titre vectors and compositions used in such methods

A retroviral vector derived from a non-primate lentivirus genome comprising a deleted gag gene wherein the deletion in gag removes one or more nucleotides downstream of nucleotide 350 of the gag coding sequence.

Equine infectious anemia virus vectors

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Jonathan Rohll