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US 12,516,326 B2Granted
Viral vectors for treating neurogenic detrusor overactivity
AssigneesUniversite De Versailles-St Quentin En Yvelines, Assistance Publique-Hopitaux de Paris
InventorsFrançois Giuliano, Alberto Epstein, Olivier Le Coz, Alejandro Aranda
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Abstract
The present invention provides a method and a pharmaceutical composition for the treatment of the NDO comprising the viral expression vector carrying a transcription cassette that harbors transgene(s) inhibiting/silencing neurotransmission or synaptic transmission of afferent neurons.
Claims8
A herpes simplex virus 1 (HSV-1) viral expression vector comprising at least:
- a) one promoter active selectively in afferent neurons of the bladder, wherein said promoter active selectively in afferent neurons of the bladder is a promoter of Calcitonin Gene Related Peptide (CGRP);
- b) at least one transcription cassette comprising a nucleotide sequence operably linked to said promoter,
- wherein said nucleotide sequence prevents the neurotransmitter filled synaptic vesicles from attaching to the presynaptic membrane, therefore inhibiting exocytosis of the neurotransmitter from the presynaptic nerve terminal, and
- wherein said nucleotide sequence codes for a wild-type or a modified bacterial neurotoxin light chain of Clostridium tetani or botulinum or for an active fragment thereof disrupting the SNARE complex or an active fragment thereof;
- and
- c) one sequence conferring long-term expression, wherein said long-term expression sequence is an LTE and a DNA insulator from the HSV-1 genome and wherein said transcription cassette is placed between the LTE and the DNA insulator.
3 more elements
Dependencies are inferred from the claim text.