Abstract: A cell for producing retroviral vectors comprising nucleic acid sequences encoding: i) gag-pol; ii) env; iii) the RNA genome of the retroviral vector; and iv) optionally rev, or a functional substitute thereof, wherein at least two nucleic acid sequences are located at the same genetic locus; and wherein the at least two nucleic acid sequences are in reverse and/or alternating orientations.

Abstract: A method of improving motor function and reducing dyskinesia in a subject suffering from a neurodegenerative disease or a disease where endogenous dopamine levels are reduced in the subject comprising administering an effective amount of a viral vector comprising a nucleic acid construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1), (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC), or any combination thereof to the subject.

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: Disclosed herein are viral vector production systems secreting nuclease for degradation of residual nucleic acid during viral vector production and methods of the same. Such a viral vector production system comprises a viral vector production cell comprising nucleic acid sequences encoding: 1) viral vector components; and 2) a nuclease, wherein the nuclease is expressed in the production cell and secreted in cell culture thereby degrading residual nucleic acid during viral vector production. Another such viral vector production system comprises 1) a viral vector production cell comprising nucleic acid sequences encoding viral vector components; and 2) a nuclease helper cell comprising a nucleic acid sequence encoding a nuclease, wherein the nuclease is expressed and secreted in co-culture of the production cell of 1) and the helper cell of 2), thereby degrading residual nucleic acid during viral vector production.

Abstract: The present invention relates to a nucleic acid sequence comprising a binding site operably linked to a nucleotide of interest, wherein the binding site is capable of interacting with an RNA-binding protein such that translation of the nucleotide of interest is repressed in a viral vector production cell.

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 nucleic acid sequence comprising a binding site operably linked to a nucleotide of interest, wherein the binding site is capable of interacting with an RNA-binding protein such that translation of the nucleotide of interest is repressed in a viral vector production cell.

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: A cell for producing retroviral vectors comprising nucleic acid sequences encoding: i) gag-pol; ii) env; iii) the RNA genome of the retroviral vector; and iv) optionally rev, or a functional substitute thereof, wherein at least two nucleic acid sequences are located at the same genetic locus; and wherein the at least two nucleic acid sequences are in reverse and/or alternating orientations.

Abstract: A process for producing a retroviral or lentiviral vector formulation comprising a filter-sterilisation step wherein the filter-sterilisation step is not the final step in the purification process.

Abstract: Provided is a multicistronic retroviral vector genome having a first nucleic acid sequence upstream of at least one internal regulatory element, such that the level of genomic RNA available for packaging in the absence of rev, or a functional equivalent thereof, is increased.

Abstract: A process for producing a retroviral or lentiviral vector formulation comprising a filter-sterilisation step wherein the filter-sterilisation step is not the final step in the purification process.

Abstract: A process for producing a retroviral or lentiviral vector formulation comprising a filter-sterilisation step wherein the filter-sterilisation step is not the final step in the purification process.

Abstract: The present invention relates to a nucleic acid sequence comprising a binding site operably linked to a nucleotide of interest, wherein the binding site is capable of interacting with an RNA-binding protein such that translation of the nucleotide of interest is repressed in a viral vector production cell.

Abstract: Provided is a lentiviral vector for delivery to the brain for use in treating a neurological condition, wherein the lentiviral vector is delivered directly to the brain by delivering the lentiviral vector via six or fewer tracts per hemisphere, at a single deposit point per tract.

Abstract: A process for producing a retroviral or lentiviral vector formulation comprising a filter-sterilization step wherein the filter-sterilization step is not the final step in the purification process.

Abstract: Provided is a lentiviral vector for delivery to the brain for use in treating a neurological condition, wherein the lentiviral vector is delivered directly to the brain by delivering the lentiviral vector via six or fewer tracts per hemisphere, at a single deposit point per tract.

Abstract: Provided is an improved treatment for Parkinson's Disease where the efficacy of L-Dopa treatment is increased by including gene therapy in the treatment regimen. The combination therapy results in long-term improvements in response to L-Dopa and diminished side effects caused by L-Dopa.

Abstract: Provided is a lentiviral vector for delivery to the brain for use in treating a neurological condition, wherein the lentiviral vector is delivered directly to the brain by delivering the lentiviral vector via six or fewer tracts per hemisphere, at a single deposit point per tract.

Abstract: The present invention provides methods for: (i) treating and/or preventing Parkinson's disease in a subject without causing cognitive impairment by using dopamine replacement gene therapy to maintain or restore constant physiological dopaminergic tone in both the dorsal and ventral striatum of the subject; (ii) normalising neuronal electrical activity in basal ganglia and/or subthalamic nucleus in a Parkinson's disease subject; and (iii) treating and/or preventing dyskinesias associated with oral L-dopa administration in a Parkinson's disease subject by administration of a vector system for dopamine replacement gene therapy to the subject.