Abstract: Provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding TH is linked to the nucleotide sequence encoding CH1 such that they encode a fusion protein TH-CH1. Also provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding AADC is linked to the nucleotide sequence encoding TH such that they encode a fusion protein AADC-TH or TH-AADC. Further provided is a viral vector comprising such nucleotide sequences and its use in the treatment and/or prevention of Parkinson's disease.

Abstract: Provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding TH is linked to the nucleotide sequence encoding CH1 such that they encode a fusion protein TH-CH1. Also provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding AADC is linked to the nucleotide sequence encoding TH such that they encode a fusion protein AADC-TH or TH-AADC. Further provided is a viral vector comprising such nucleotide sequences and its use in the treatment and/or prevention of Parkinson's disease.

Abstract: Provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding TH is linked to the nucleotide sequence encoding CH1 such that they encode a fusion protein TH-CH1. Also provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding AADC is linked to the nucleotide sequence encoding TH such that they encode a fusion protein AADC-TH or TH-AADC. Further provided is a viral vector comprising such nucleotide sequences and its use in the treatment and/or prevention of Parkinson's disease.

Abstract: The present invention relates to a novel method for the delivery of agents to tumour cells. In particular it relates to a method for the specific delivery of agents to the interior of tumour cells. Uses of the method are also described.

Abstract: A method of producing a replication defective retrovirus comprising transfecting a producer cell with the following: iii) a retroviral genome; iv) a nucleotide sequence coding for retroviral gag and pot proteins; and iii) nucleotide sequences encoding other essential viral packaging components not encoded by the nucleotide sequence of (ii); characterised in that the nucleotide sequence coding for retroviral gag and pot proteins is codon optimised for expression in the producer cell.

Abstract: A viral vector production system is provided which system comprises: (i) a viral genome comprising at least one first nucleotide sequence encoding a gene product capable of binding to and effecting the cleavage, directly or indirectly, of a second nucleotide sequence, or transcription product thereof, encoding a viral polypeptide required for the assembly of viral particles; (ii) a third nucleotide sequence encoding said viral polypeptide required for the assembly of the viral genome into viral particles, which third nucleotide sequence has a different nucleotide sequence to the second nucleotide sequence such that said third nucleotide sequence, or transcription product thereof, is resistant to cleavage directed by said gene product. The viral vector production system may be used to produce viral particles for use in treating or preventing viral infection.

Abstract: The present invention provides a vector system comprising a nucleotide sequence coding for an antibody. In particular, the present invention relates to the use of such a vector system in a subject, where the nucleotide sequence is expressed in vivo to produce said antibody.

Abstract: Retroviral vector production systems for producing lentivirus-based vector particles which are capable of infecting and transducing non-dividing target cells, wherein one or more of the auxiliary genes such as vpr, vif, tat, and nef in the case of HIV-1 are absent from the system. The systems and resulting retrovirus vector particles have improved safety over existing systems and vectors.

Abstract: A method of producing a replication defective retrovirus comprising transfecting a producer cell with the following: iii) a retroviral genome; iv) a nucleotide sequence coding for retroviral gag and pol proteins; and iii) nucleotide sequences encoding other essential viral packaging components not encoded by the nucleotide sequence of (ii); characterised in that the nucleotide sequence coding for retroviral gag and pol proteins is codon optimised for expression in the producer cell.

Abstract: A retroviral vector is described. The retroviral vector comprises a functional splice donor site and a functional splice acceptor site; wherein the functional splice donor site and the functional splice acceptor site flank a first nucleotide sequence of interest (“NOI”); wherein the functional splice donor site is upstream of the functional splice acceptor site; wherein the retroviral vector is derived from a retroviral pro-vector; wherein the retroviral pro-vector comprises a first nucleotide sequence (“NS”) capable of yielding the functional splice donor site and a second NS capable of yielding the functional splice acceptor site; wherein the first NS is downstream of the second NS; such that the retroviral vector is formed as a result of reverse transcription of the retroviral pro-vector.

Abstract: 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.

Abstract: Retroviral vector production systems for producing lentivirus-based vector particles which are capable of infecting and transducing non-dividing target cells, wherein one or more of the auxiliary genes such as vpr, vif, tat, and nef in the case of HIV-1 are absent from the system. The systems and resulting retrovirus vector particles have improved safety over existing systems and vectors.

Abstract: A vector capable of transducing non-dividing and/or slowly dividing cells is provided, wherein the vector is a lentiviral LTR-deleted vector. Also provided is a method for producing a protein of interest in a non-dividing or slowly dividing cell by transducing the cell with a lentiviral LTR-deleted vector and expressing the protein of interest in the cell. In addition, target cells containing the lentiviral LTR-deleted vector are provided.

Abstract: 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.

Abstract: A vector capable of transducing non-dividing and/or slowly dividing cells is provided, wherein the vector is a lentiviral LTR-deleted vector. Also provided is a method for producing a protein of interest in a non-dividing or slowly dividing cell by transducing the cell with a lentiviral LTR-deleted vector and expressing the protein of interest in the cell. In addition, target cells containing the lentiviral LTR-deleted vector are provided.

Abstract: A retroviral vector is described. The retroviral vector comprises a functional splice donor site and a functional splice acceptor site; wherein the functional splice donor site and the functional splice acceptor site flank a first nucleotide sequence of interest (“NOI”); wherein the functional splice donor site is upstream of the functional splice acceptor site; wherein the retroviral vector is derived from a retroviral pro-vector; wherein the retroviral pro-vector comprises a first nucleotide sequence (“NS”) capable of yielding the functional splice donor site and a second NS capable of yielding the functional splice acceptor site; wherein the first NS is downstream of the second NS; such that the retroviral vector is formed as a result of reverse transcription of the retroviral pro-vector.

Abstract: The present invention provides a vector system comprising a nucleotide sequence coding for an antibody. In particular, the present invention relates to the use of such a vector system in a subject, where the nucleotide sequence is expressed in vivo to produce said antibody.

Abstract: Retroviral vector production systems for producing lentivirus-based vector particles which are capable of infecting and transducing non-dividing target cells, wherein one or more of the auxiliary genes such as vpr, vif, tat, and nef in the case of HIV-1 are absent from the system. The systems and resulting retrovirus vector particles have improved safety over existing systems and vectors.

Abstract: 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.

Abstract: A viral vector production system is provided which system comprises: