Gene therapies for neurodegenerative diseases
AssigneePrevail Therapeutics, Inc.
InventorsAsa Abeliovich, Laura Heckman, Herve Rhinn
Life of this patent
Estimating the term…
Abstract
The disclosure relates, in some aspects, to compositions and methods for treatment of neurodegenerative diseases (e.g., amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD), Alzheimer's disease, Gaucher disease, Parkinson's disease, Lewy body dementia, or a lysosomal storage disease). In some embodiments, the disclosure provides expression constructs comprising a transgene encoding one or more inhibitory nucleic acids (e.g., targeting C9orf72, TMEM106B, ATNX2, RPS25, etc.), wild-type C9orf72 protein or a portion thereof, or any combination of the foregoing. In some embodiments, the disclosure provides methods of ALS/FTD by administering such expression constructs to a subject in need thereof.
Claims49
1-90. (canceled)
An isolated nucleic acid comprising
- (i) an expression construct comprises a transgene encoding:
- (a) a C9Orf72 protein encoded by the sequence set forth in SEQ ID NO:
- 51 and (b) an inhibitory nucleic acid that inhibits expression or activity of C9orf72, and
- (ii) two adeno-associated virus inverted terminal repeats (ITR) sequences flanking the expression construct.
A recombinant adeno-associated virus (AAV) vector comprising an expression construct comprises a transgene encoding:
- (i) a C9Orf72 protein encoded by the sequence set forth in SEQ ID NO:
- 51;
- and
- (ii) an inhibitory nucleic acid that inhibits expression or activity of C9orf72;
- wherein the expression construct is flanked by two adeno-associated virus (AAV) inverted terminal repeats (ITRs).
A recombinant adeno-associated virus (AAV) vector comprising a nucleic acid comprising, in 5′ to 3′ order:
- (a) a 5′ AAV ITR;
- (b) a CMV enhancer;
- (c) a CBA promoter;
- (d) a transgene encoding a C9Orf72 protein, wherein the C9Orf72 protein is encoded by the nucleic acid sequence in SEQ ID NO:
- 51, and an inhibitory nucleic acid that inhibits expression or activity of C9orf72;
- (e) a WPRE;
- (f) a Bovine Growth Hormone polyA signal tail;
- and
- (g) a 3′ AAV ITR.
A Baculovirus vector comprising (i) the nucleic acid sequence set forth in SEQ ID NO:
- 51, and (ii) a nucleic acid sequence encoding an inhibitory nucleic acid that inhibits expression or activity of C9orf72.
A cell comprising:
- (i) a first vector encoding one or more adeno-associated virus rep protein and/or one or more adeno-associated virus cap protein;
- and
- (ii) a second vector comprising an expression construct encoding a C9Orf72 protein encoded by the sequence set forth in SEQ ID NO:
- 51 and an inhibitory nucleic acid that inhibits expression or activity of C9orf72.
Dependencies are inferred from the claim text.