Abstract: This disclosure concerns transcription cassettes comprising nucleic acid molecules comprising a nucleotide sequence encoding AP-4 subunits; vectors comprising said transcription cassettes; pharmaceutical compositions comprising said vector; and vectors or compositions for use in the treatment of AP-4-Hereditary Spastic Paraplegia.

Abstract: The present disclosure relates to transcription cassettes comprising nucleic acids encoding RuvBL1 and/or RuvBL2 and the use of said vectors in gene therapy for the treatment of neurodegenerative diseases that result from expression of polymorphic repeat expansions of the GGGGCC (SEQ ID NO: 5) hexanucleotide-repeat sequence in the first intron of the C9ORF72 gene; pharmaceutical compositions comprising said vectors and including uses and methods to treat neurodegenerative diseases.

Abstract: The present disclosure relates to antagonists that target Serine/Arginine-Rich Splicing Factor 1 (SRSF1); expression vectors comprising SRSF1 antagonists; and the use of such antagonists in therapy for the treatment of neurodegenerative disorders and cancer and screening methods that identify agents that inhibit the expression or activity of SRSF1.

Abstract: The present disclosure relates to antagonists that target Serine/Arginine-Rich Splicing Factor 1 (SRSF1); expression vectors comprising SRSF1 antagonists; and the use of such antagonists in therapy for the treatment of neurodegenerative disorders and cancer and screening methods that identify agents that inhibit the expression or activity of SRSF1.

Abstract: Provided is a method of treating motor neuron disease using a lentiviral vector system to transduce a target site, wherein the vector system is or comprises at least part of a rabies G envelope protein or a mutant, variant, homologue or fragment thereof, and a nucleotide of interest (NOI), and wherein the target site is at least part of the central nervous system.

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: Provided is a method for treating and/or preventing pain, in which a vector system is administered such that an EOI is delivered to a DRG of the subject. Also provided is a method for delivering an EOI to the spinal cord using such a vector system. Further provided is a method for identifying and/or validating an EOI by delivering a test EOI to target cell; analyzing the effect of the EOI on the target cell; and selecting an EOI with therapeutic potential. An EOI identified or validated by such a method, useful in the prevention and/or treatment of pain, is thereby provided as well.

Abstract: The present invention relates to retroviral vector genomes and to vector systems comprising such genomes. In particular the present invention relates to 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.

Abstract: Provided is a method for treating and/or preventing pain, in which a vector system is administered such that an EOI is delivered to a DRG of the subject. Also provided is a method for delivering an EOI to the spinal cord using such a vector system. Further provided is a method for identifying and/or validating an EOI by delivering a test EOI to target cell; analyzing the effect of the EOI on the target cell; and selecting an EOI with therapeutic potential. An EOI identified or validated by such a method, useful in the prevention and/or treatment of pain, is thereby provided as well.

Abstract: Provided is a method of treating motor neuron disease using a lentiviral vector system to transduce a target site, wherein the vector system is or comprises at least part of a rabies G envelope protein or a mutant, variant, homologue or fragment thereof, and a nucleotide of interest (NOI), and wherein the target site is at least part of the central nervous system.

Abstract: There is provided the use of a vector system comprising at least part of a rabies g protein, to transduce a TH positive neuron. There is also provided the use of a rabies G vector system to transduce a target site, in which the vector system travels to the target site by retrograde transport, which may comprise the step of administration of the vector system to an administration site which is distant from the target site.

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.