Gene therapy for treating propionic acidemia
AssigneeUltragenyx Pharmaceutical Inc.
InventorsMatthew Scott Fuller, Samuel Wadsworth, Kelly Reed Clark, Sean Christopher Daugherty, Stewart Craig
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Abstract
This present disclosure provides adeno-associated viral vectors, recombinant adeno-associated virus (rAAV), and methods of their use in gene therapy for treating propionic acidemia (PA). Also provided are pharmaceutical compositions comprising a recombinant adeno-associated virus of the invention and a pharmaceutically acceptable carrier or excipient. These pharmaceutical (compositions may be useful in gene therapy for the treatment of PA caused by mutations in propionyl-CoA carboxylase α-subunit (PCCA) or mutations in propionyl-CoA carboxylase β-subunit (PCCB).
Claims28
A recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising in 5′ to 3′ order:
- (a) a 5′-inverted terminal repeat sequence (5′-ITR) sequence;
- (b) a promoter sequence;
- (c) a human beta globin IVS2 intron sequence;
- (d) a wild type coding sequence for propionyl-CoA carboxylase B (PCCB) according to SEQ ID NO:
- 7;
- and
- (e) a 3′-inverted terminal repeat sequence (3′-ITR) sequence.
A recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising in 5′ to 3′ order:
- (a) a 5′-ITR sequence;
- (b) an enhancer sequence;
- (c) a promoter sequence;
- (d) a human beta globin IVS2 intron sequence;
- (e) wild type coding sequence for propionyl-CoA carboxylase B (PCCB) according to SEQ ID NO:
- 7;
- (f) a polyadenylation signal sequence;
- and
- (g) a 3′-ITR sequence.
A recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising in 5′ to 3′ order:
- (a) an AAV2 5′-inverted terminal repeat sequence (ITR) sequence;
- (b) a cytomegalovirus (CMV) immediate early gene enhancer sequence;
- (c) a chicken β-actin (CBA) promoter sequence;
- (d) a human beta globin IVS2 intron sequence;
- (e) a wild type coding sequence for propionyl-CoA carboxylase B (PCCB) according to SEQ ID NO:
- 7;
- (f) a BGH or an SV40 polyadenylation signal sequence;
- and
- (g) an AAV2 3′-inverted terminal repeat sequence (ITR) sequence.
A recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV9 capsid, and a vector genome packaged therein, said vector genome comprising in 5′ to 3′ order:
- (a) a 5′-inverted terminal repeat sequence (ITR) sequence;
- (b) an enhancer sequence;
- (c) a promoter sequence;
- (d) a human beta globin IVS2 intron sequence;
- (e) a wild type coding sequence for propionyl-CoA carboxylase B (PCCB) according to SEQ ID NO:
- 7;
- (f) a polyadenylation signal sequence;
- and
- (g) a 3′-inverted terminal repeat sequence (ITR) sequence.
A recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV9 capsid, and a vector genome packaged therein, said vector genome comprising in 5′ to 3′ order:
- (a) an AAV2 5′-inverted terminal repeat sequence (ITR) sequence;
- (b) a cytomegalovirus (CMV) immediate early gene enhancer sequence;
- (c) a chicken β-actin (CBA) promoter sequence;
- (d) a human beta globin IVS2 intron sequence;
- (e) a wild type coding sequence for propionyl-CoA carboxylase B (PCCB) according to SEQ ID NO:
- 7;
- (f) a BGH or an SV40 polyadenylation signal sequence;
- and
- (g) an AAV2 3′-inverted terminal repeat sequence (ITR) sequence.
Dependencies are inferred from the claim text.