Recombinant parvovirus vectors and method of making
AssigneeThe University of North Carolina at Chapel Hill
InventorsJoseph E. Rabinowitz, Richard Jude Samulski, Weidong Xiao
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Abstract
The present invention provides genetically-engineered parvovirus capsids and viruses designed to introduce a heterologous gene into a target cell. The parvoviruses of the invention provide a repertoire of vectors with altered antigenic properties, packaging capabilities, and/or cellular tropisms as compared with current AAV vectors.
Claims71
A chimeric virus particle comprising:
- (a) a chimeric parvovirus capsid comprising at least one capsid region from an adeno-associated virus (AAV) and at least one capsid region from a B19 virus;
- and
- (b) an AAV genome comprising 5′ and 3′ AAV inverted terminal repeats, wherein said AAV genome is packaged within said chimeric parvovirus capsid.
A chimeric virus particle comprising:
- (a) a chimeric parvovirus capsid comprising a chimeric parvovirus capsid protein comprising at least one capsid region from a different parvovirus;
- and
- (b) an AAV genome comprising 5′ and 3′ AAV inverted terminal repeats, wherein said AAV genome is packaged within the chimeric parvovirus capsid.
A chimeric virus particle comprising:
- (a) a chimeric adeno-associated virus (AAV) capsid comprising at least one capsid region from a different parvovirus;
- and
- (b) an AAV genome comprising 5′ and 3′ AAV inverted terminal repeats, wherein said AAV genome is packaged within the chimeric AAV capsid.
An isolated nucleic acid encoding the adeno-associated virus (AAV) cap genes and the AAV rep genes, wherein the AAV cap genes encode a chimeric AAV capsid protein comprising at least one capsid region from a different parvovirus.
A method of producing a chimeric virus particle, comprising:
- providing a cell with parvovirus cap genes, rep genes from an adeno-associated virus (AAV), an AAV genome comprising at least one AAV inverted terminal repeat, and helper functions for generating a productive AAV infection;
- wherein the cap genes are chimeric comprising at least one nucleic acid sequence from the cap genes of a different parvovirus such that the chimeric cap genes encode a chimeric parvovirus capsid comprising at least one capsid region from a different parvovirus;
- and
- allowing assembly of the chimeric virus particles.
A method of delivering a nucleic acid sequence to a cell in culture, comprising:
- introducing into a cell in culture a chimeric virus particle comprising a parvovirus capsid and an adeno-associated virus (AAV) genome comprising 5′ and 3′ AAV inverted terminal repeats, wherein the AAV genome is packaged within the capsid,
- wherein the parvovirus capsid comprises at least one capsid region from a different parvovirus.
A method of delivering a nucleic acid sequence to a cell in culture, comprising:
- introducing into a cell in culture a chimeric virus particle comprising an adeno-associated virus (AAV) capsid and an AAV genome comprising 5′ and 3′ AAV inverted terminal repeats, wherein the AAV genome is packaged within the AAV capsid,
- wherein the AAV capsid comprises at least one capsid region from a different parvovirus.
A chimeric virus particle comprising:
- (a) a chimeric parvovirus capsid comprising a chimeric parvovirus capsid comprising at least one capsid region from a different parvovirus, wherein said at least one capsid region from said different parvovirus replaces a capsid subunit in said parvovirus capsid;
- and
- (b) an AAV genome comprising 5′ and 3′ AAV inverted terminal repeats, wherein said AAV genome is packaged within the chimeric parvovirus capsid.
Dependencies are inferred from the claim text.