Replication incompetent herpes viruses for use in gene therapy
AssigneeBiovex Limited
InventorRobert Stuart Coffin
Life of this patent
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Abstract
Use of a replication incompetent herpes virus capable of delivering a gene to multiple connected sites within the nervous system, which virus comprises: (a) a mutation which prevents or reduces the expression of at least two immediate early genes; and (b) a heterologous gene operably linked to a promoter active during herpes virus latency; in the manufacture of a medicament for the treatment of a central nervous system disorder, a method of determining whether a gene has an effect on a phenotype associated with a central nervous system disorder and in a method of treatment of a disorder of the central nervous system are described.
Claims34
Use of a replication incompetent herpes virus comprising:
- (a) a mutation which prevents or reduces to minimal levels the expression of ICP27, ICP4, ICP22 and ICP0;
- and
- (b) a heterologous gene operably linked to a promoter active during herpes virus latency in the manufacture of a medicament for use in treating or preventing a central nervous system disorder.
A use according to any one of the preceding claims, wherein said virus lacks functional genes encoding ICP27, ICP4, ICP0 and ICP22.
A use according to any one of the preceding claims, wherein said virus is a herpes simplex virus 1.
A use according to any one of the preceding claims, wherein said promoter is chimeric promoter containing elements of a latency associated transcript (LAT) region of a herpes virus and a non-LAT promoter.
A use according to any preceding claim, wherein said promoter is or contains elements from the LAP2 HSV promoter.
A use according to anyone of the preceding claims, wherein said promoter contains non-HSV elements such as an internal ribosome entry site (IRES) sequence or other sequence capable of performing a similar function.
A use according to any one of the preceding claims, wherein said heterologous gene encodes a polypeptide of therapeutic use.
A use according to any one of the preceding claims wherein said medicament is for delivery of a gene to two or more connected sites in the central nervous system by administration to a single site in the nervous system.
A use according to any one of the preceding claims wherein said medicament is for injection into the striatum or the ventricles within the brain.
A method of determining whether a gene has an effect on a phenotype associated with a central nervous system disorder or on a cell of the central nervous system which is relevant to a central nervous system disorder, which method comprises:
- (i) , inoculating into a cell of the central nervous system with a replication incompetent herpes virus comprising:
- (a) a mutation which prevents or reduces to minimal levels the expression of ICP27, ICP4, ICP22 and ICP0;
- and
- (b) a heterologous gene operably liked to a promoter active during herpes virus latency;
- and
- (ii) monitoring a phenotype of said disorder or an effect of expression of said gene on said cell to determine thereby whether said gene has an effect on said cell or said phenotype.
A method of screening genes implicated in a central nervous system disorder to identify a target for gene therapy or for small molecule modulators, which method comprises a method according to any one of the preceding claims.
A method of treating a subject suffering from a disorder of the central nervous system, or of preventing a disorder of the central nervous system in a subject at risk thereof, which method comprises administering a therapeutically effective amount of a replication incompetent herpes virus comprising:
- (a) a mutation which prevents or reduces to minimal levels the expression of ICP27, ICP4, ICP22 and ICP0;
- and
- (b) a heterologous gene operably linked to a promoter active during herpes virus latency to a subject suffering from a disorder of central nervous system.
An agent for treating or preventing a disorder of the central nervous system comprising a replication incompetent herpes virus comprising:
- (a) a mutation which prevents or reduces to minimal levels the expression of ICP27, ICP4, ICP22 and ICP0;
- and
- (b) a heterologous gene operably linked to a promoter active during herpes virus latency.
Dependencies are inferred from the claim text.