Herpes simplex virus amplicon vector targeting system and method of using same
AssigneesThe General Hospital Corporation, The Regents of the University of California
InventorsMatthew A. Spear, Xandra O. Breakefield
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Abstract
The present invention relates to herpes simplex virus (HSV) amplicon vectors, and in particular, HSV-1 amplicon vectors, which have been genetically modified and used alone or with consequent genetically modified HSV virus, to target a selected cell type, such as neoplastic cells. The present invention also relates to methods of using such vectors to target a cell, in order to treat a pathologic condition, such as cancer.
Claims40
A Herpes Simplex Virus (HSV) amplicon plasmid comprising:
- (a) an origin of replication,
- (b) a packaging sequence, and
- (c) a nucleotide sequence that encodes HSV glycoprotein C (gC) modified with a targeting domain;
- wherein said HSV amplicon plasmid is capable of producing an HSV virion that is capable of targeting a target cell.
An HSV amplicon plasmid comprising:
- (a) an origin of replication,
- (b) a packaging sequence, and
- (c) a nucleotide sequence encoding a modified glycoprotein C (gC), wherein the nucleotide sequence that encodes the heparan sulfate binding domain (HSBD) of gC is flanked by at least two unique restriction sites that allow said nucleotide sequence that encodes the HSBD of gC to be replaced with a targeting domain sequence, thereby allowing said amplicon plasmid to produce an HSV virion that is capable of targeting a target cell.
An HSV amplicon plasmid comprising:
- (a) an origin of replication,
- (b) a packaging sequence, and
- (c) a nucleotide sequence encoding a modified gC, wherein the nucleotide sequence that encodes the HSBD of gC is replaced with a nucleotide sequence that encodes a labeling ligand comprising an amino acid sequence that can be used to facilitate purification or detection of an amplicon vector;
- wherein said HSV amplicon plasmid is capable of producing an HSV virion that can be traced or purified by contacting said labeling ligand with a compound or matrix that specifically interacts with said labeling ligand.
A method of producing an HSV virion capable of targeting a target cell, said method comprising:
- (a) transfecting a suitable cell line with an HSV amplicon plasmid comprising:
- (i) an origin of replication, (ii) a packaging sequence, and (iii) a nucleotide sequence that encodes HSV glycoprotein C (gC) modified with a targeting domain;
- and
- (b) harvesting said HSV virion.
The HSV-1 amplicon plasmid pCONGA.
The HSV-1 amplicon plasmid pCONGAH.
The HSV-1 amplicon plasmid pCONGA4.
Dependencies are inferred from the claim text.