HSV/AAV hybrid amplicon vectors
AssigneeThe General Hospital Corporation
InventorsXandra O. Breakefield, David R. Jacoby, Frances I. Smith
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Abstract
The present invention relates to a hybrid vector system which incorporates elements of herpesvirus and adeno-associated virus and which is capable of expressing a gene product in eukaryotic cells. The vector system of the present invention provides a means of packaging plasmid DNA into highly infectious virions which can efficiently and safely deliver large transgenes to both mitotic and postmitotic cells in a state which can be maintained for extended periods. The invention pertains to the use of this vector system in introducing and expressing gene sequences in mitotic and postmitotic cells.
Claims10
A hybrid gene vector for expressing a polynucleotide sequence of interest, comprising,
- (i) a polynucleotide sequence of interest in operable linkage with a promoter;
- (ii) a subset of viral polynucleotide sequences from a herpesvirus comprising a herpesviral origin of replication and packaging signal sufficient for replication and packaging of the vector in herpesviral virions, and;
- (iii) a subset of viral polynucleotide sequences from an adeno-associated virus (AAV) comprising AAV elements sufficient to increase persistence of the vector in mitotic and non-mitotic cells;
- wherein said polynucleotide sequences are in operable association for expressing said polynucleotide sequence of interest.
A hybrid vector for expressing a transgene comprising,
- (a) a DNA sequence derived from a Herpes Simplex Virus (HSV) comprising a HSV origin of DNA replication and packaging signal;
- and
- (b) inverted terminal repeat sequences from Adeno-Associated Virus (AAV) flanking a transgene cassette, wherein said transgene cassette comprises a polynucleotide sequence of interest operably linked to a promoter;
- wherein said sequences are in operable association for expressing said transgene.
A hybrid vector for expressing a transgene comprising,
- (a) a DNA sequence derived from a Herpes Simplex Virus (HSV) comprising a HSV origin of DNA replication and packaging signal;
- (b) inverted terminal repeat sequences from Adeno-Associated Virus (AAV) flanking a transgene cassette, wherein said transgene cassette comprises a polynucleotide sequence of interest operably linked to a promoter;
- and
- (c) an AAV rep gene inserted outside the inverted terminal repeat flanked transgene cassette;
- wherein said sequences are in operable association for expressing said transgene.
Dependencies are inferred from the claim text.