Duplexed parvovirus vectors
AssigneeThe University of North Carolina at Chapel Hill
InventorsRichard Jude Samulski, Douglas M. McCarty
Life of this patent
Estimating the term…
Abstract
The present invention provides duplexed parvovirus vector genomes that are capable under appropriate conditions of forming a double-stranded molecule by intrastrand base-pairing. Also provided are duplexed parvovirus particles comprising the vector genome. Further disclosed are templates and methods for producing the duplexed vector genomes and duplexed parvovirus particles of the invention. Methods of administering these reagents to a cell or subject are also described. Preferably, the parvovirus capsid is an AAV capsid. It is further preferred that the vector genome comprises AAV terminal repeat sequences.
Claims18
An adeno-associated virus (AAV) particle comprising:
- an AAV capsid;
- and
- a vector genome comprising in the 5′ to 3′ direction:
- (i) a 5′ AAV terminal repeat;
- (ii) a first heterologous nucleotide sequence;
- (iii) an AAV inverted terminal repeat that forms a hairpin structure, does not comprise a functional AAV terminal resolution site (trs), and is resolved by Rep protein to a lesser extent as compared with the 5′ AAV terminal repeat and a 3′ AAV terminal repeat;
- (iv) a separate heterologous nucleotide sequence;
- and
- (v) the 3′ AAV terminal repeat;
- wherein the first and the separate heterologous nucleotide sequences are essentially self-complementary and form a double-stranded nucleic acid sequence that encodes a factor IX polypeptide.
An AAV particle comprising:
- an AAV capsid;
- and
- a vector genome comprising in the 5′ to 3′ direction:
- (i) a 5′ AAV terminal repeat;
- (ii) a first heterologous nucleotide sequence;
- (iii) an AAV terminal repeat modified such that it does not comprise a functional AAV trs and such that resolution by Rep protein is reduced as compared with the 5′ AAV terminal repeat and a 3′ AAV terminal repeat;
- (iv) a separate heterologous nucleotide sequence;
- and
- (v) the 3′ AAV terminal repeat;
- wherein the first and the separate heterologous nucleotide sequences are essentially self-complementary and may form a hairpin structure, and form a double-stranded nucleic acid sequence that encodes a factor IX polypeptide.
Dependencies are inferred from the claim text.