Gene therapies for lysosomal disorders
AssigneePrevail Therapeutics, Inc.
InventorsAsa Abeliovich, Laura Heckman, Herve Rhinn
Life of this patent
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Abstract
The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof, Lysosomal Membrane Protein 2 (LIMP2), Prosaposin, or any combination of the foregoing. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.
Claims23
An isolated nucleic acid comprising:
- (i) an expression construct comprising a promoter operably linked to a transgene insert encoding a beta-glucocerebrosidase (Gcase) protein, wherein the transgene insert comprises the nucleotide sequence of SEQ ID NO:
- 15;
- and (ii) two adeno-associated virus (AAV) inverted terminal repeat (ITR) sequences flanking the expression construct, wherein the first ITR sequence is a 5′ ITR, and the second ITR sequence is a 3′ ITR.
An isolated nucleic acid comprising, in 5′ to 3′ order:
- (a) a 5′ AAV ITR;
- (b) a CMVe;
- (c) a CBA promoter;
- (d) a transgene insert encoding a Gcase protein, wherein the transgene insert comprises the nucleotide sequence of SEQ ID NO:
- 15;
- (e) a WPRE;
- (f) a Bovine Growth Hormone polyA signal tail;
- and
- (g) a 3′ AAV ITR.
A plasmid comprising a nucleic acid comprising:
- (i) an expression construct comprising a promoter operably linked to a transgene insert encoding a Gcase protein, wherein the transgene insert comprises the nucleotide sequence of SEQ ID NO:
- 15;
- and
- (ii) two AAV ITR sequences flanking the expression construct.
A Baculovirus vector comprising a nucleic acid comprising:
- (i) an expression construct comprising a promoter operably linked to a transgene insert encoding a Gcase protein, wherein the transgene insert comprises the nucleotide sequence of SEQ ID NO:
- 15;
- and
- (ii) two AAV ITR sequences flanking the expression construct.
An isolated cell comprising:
- (i) a first vector encoding one or more AAV rep proteins and/or one or more AAV cap proteins;
- and
- (ii) a second vector comprising a nucleic acid comprising:
- (a) an expression construct comprising a promoter operably linked to a transgene insert encoding a Gcase protein, wherein the transgene insert comprises the nucleotide sequence of SEQ ID NO:
- 15;
- and
- (b) two AAV ITR sequences flanking the expression construct.
A rAAV vector comprising a nucleic acid comprising an expression construct comprising a promoter operably linked to a transgene insert encoding a Gcase protein, wherein the transgene insert is SEQ ID NO:
- 15.
Dependencies are inferred from the claim text.