Inducible single aav system and uses thereof
AssigneeUniversity of Massachusetts
InventorChristian Mueller
Life of this patent
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Abstract
Aspects of the disclosure relate to compositions and methods for epigenetic regulation of endogenous gene expression from viral vectors. In some embodiments, the disclosure provides expression constructs comprising a viral vector encoding a transgene, the activation of which is regulated by a rapamycin/rapalog-based system, and the transgene is capable of epigenetically regulate an endogenous gene.
Claims59
An isolated nucleic acid comprising an expression cassette comprising a promoter operably linked to a transgene, wherein the transgene encodes a FKBP-rapamycin binding protein (FRB), an epigenetic modulator, a rapamycin-binding protein (FKBP), and a DNA binding protein that specifically binds to an endogenous gene promoter.
A recombinant adeno-associated virus (rAAV) vector comprising, in 5′ to 3′ order:
- (a) a 5′ AAV ITR;
- (b) a promoter;
- (c) a transgene comprising, in 5′ to 3′ order:
- (A) a nucleotide sequence encoding a FRB-epigenetic modulator fusion protein;
- (B) a nucleotide sequence encoding an internal ribosome entry site (IRES);
- and
- (C) a nucleotide sequence encoding a FKBP-zinc finger domain fusion protein;
- and
- (d) a 3′ AAV ITR.
A recombinant adeno-associated virus (rAAV), comprising:
- (i) an AAV capsid protein;
- and
- (ii) an isolated nucleic acid comprising, in 5′ to 3′ order:
- (a) a 5′ AAV ITR;
- (b) a promoter;
- (c) a transgene comprising, in 5′ to 3′ order:
- (A) a nucleotide sequence encoding a FRB-epigenetic modulator fusion protein;
- (B) a nucleotide sequence encoding an internal ribosome entry site (IRES);
- and
- (C) a nucleotide sequence encoding a FKBP-zinc finger domain fusion protein;
- and
- (d) a 3′ AAV ITR.
Dependencies are inferred from the claim text.