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 differential expression screening method is provided for identifying a genetic element involved in a cellular process, which method comprises comparing:

Abstract: 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.

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 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: Polynucleotide sequences and vectors containing them, for use in gene therapy, the polynucleotide sequences comprising two or more therapeutic genes operably linked to a promoter and encoding a fusion protein product of the therapeutic genes. The fusion protein may be for example a tyrosine hydroxylase (TH)-DOPA decarboxylase (DD) fusion in either TH-DD or DD-TH order, useful for treating Parkinson's disease.

Abstract: The present invention relates to the use of RAR&bgr;2 and/or an agonist thereof in the preparation of a medicament to cause neurite development.

Abstract: Retroviral vector particles having an RNA genome carrying sequences which provide in the DNA provirus at least one selected gene located within an intron in a transcription unit of the provirus, which transcription unit further comprises a polynucleotide response element responsive to a nucleus to cytoplasm transport factor such as HIV Rev. Expression of the selected genes is thus rendered Rev-dependent and so is dependent upon the presence of HIV.

Abstract: A method is provided for selecting an improved retroviral genome having an improved packaging efficiency which method comprises: a) introducing one or more random mutations into a retroviral genome comprising a packaging signal; b) introducing the mutagenised retroviral genome into a host cell expressing viral polypeptides required for packaging the retroviral genome; c) determining whether retroviral packaging efficiency in the cell is improved as compared with a retroviral genome comprising a non-mutated packaging signal; d) selecting a viral genome which has improved packaging efficiency.

Abstract: A method is provided for enhancing the production of an infectious retrovirus comprising an envelope polypeptide in a producer cell which method comprises inhibiting the expression or activity in the producer cell of an endogenous receptor which is capable of binding to the envelope polypeptide of said retroviruses.

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 retroviral vector capable of delivering an NOI and comprising an exogenous second synthesis element.

Abstract: 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.

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: Retroviral vector particles capable of infecting and transducing non-dividing mammalian target cells, which vector particles may be based on letiviruses such as HIV and which have an RNA genome constructed so as to provide in the DNA provirus a non-lentiviral expression control element in the 5′LTR of the provirus.

Abstract: A method of making retrovirus vectors having selected characteristics, in particular an increased ability to infect a particular target cell, comprises subjecting a starting retrovirus or retroviral vector to a selection process in vitro which involves a plurality of rounds of infection of a host cell during which the retrovirus or retroviral vector evolves to attain the selected characteristics. Components of the evolved retrovirus or retroviral vector can be used in retroviral vector production systems for producing retroviral vectors having the selected characteristics. The invention is particularly useful for preparing retroviral vectors suitable for gene therapy.

Abstract: A proteinaceous particle comprises a capsid enveloped by ecotropic Murine Leukemia virus envelope proteins characterized in that a heterologous peptide which binds to a non-murine cell is inserted in, entirely replaces, or replaces a portion of the native Ser-Gly-Gly-Ser-Ser-Pro-Gly of the VRA region of said envelope proteins. A method for preparing a plurality of such proteinaceous particles comprises expressing within a host cell (i) self-assembling capsid proteins, (ii) Murine Leukemia virus envelope proteins, said ENV proteins modified as defined, and optionally, (iii) packageable RNA, and then culturing the host cells and harvesting the resultant budded particles.

Abstract: A DNA construct is disclosed which comprises a packagable retroviral genome operably linked to a first promotor, wherein the retroviral genome comprises a 5' long terminal repeat (5' LTR) which includes sequences encoding R and U3 regions and 3' long terminal repeat (3' LTR) which includes sequences encoding R and U3 regions, and wherein at least said R regions of the 5' LTR and 3' LTR are identical to each other and are different from those of the retrovirus on which the retroviral genome is based. The DNA constructs are useful in the production of packaged retroviruses.