Compositions useful in treatment of metachromatic leukodystrophy
OwnerJames M. Wilson, Juliette Hordeauxinventors
Life of this patent
Estimating the term…
Abstract
Provided is a recombinant adeno-associated virus (rAAV) having an AAVhu68 capsid and a vector genome which comprises a nucleic acid sequence encoding a functional human arylsulfatase A (ARSA). Also provided are a production system useful for producing the rAAV, a pharmaceutical composition comprising the rAAV, and a method of treating a subject having metachromatic leukodystrophy, or ameliorating symptoms of metachromatic leukodystrophy, or delaying progression of metachromatic leukodystrophy via administering an effective amount of rAAV to a subject in need thereof.
Claims28
A recombinant adeno-associated virus (rAAV), wherein the rAAV comprises:
- (a) an AAVhu68 capsid;
- and
- (b) a vector genome packaged in the AAV capsid of (a), wherein the vector genome comprises inverted terminal repeats (ITR) and a nucleic acid sequence encoding a functional human Arylsulfatase A (hARSA) operably linked to regulatory sequences which direct the hARSA expression, wherein the hARSA coding sequence comprises a nucleic acid sequence encoding a signal peptide and a sequence of nucleotide (nt) 55 to nt 1521 of SEQ ID NO:
- 1, or a sequence at least 95% to 99.9% identical thereto which encodes a functional hARSA.
A vector comprising an expression cassette, wherein the expression cassette comprises a nucleic acid sequence encoding a functional human Arylsulfatase A (hARSA) under control of regulatory sequences which direct the hARSA expression, wherein the hARSA coding sequence is SEQ ID NO:
- 1 or SEQ ID NO:
- 3, or a sequence at least 95% to 99.9% identical thereto which encodes a functional hARSA.
A method for delivering functional Arylsulfatase A (ARSA) to a subject in need thereof, comprising administering to the subject an rAAV which comprises:
- (a) an AAVhu68 capsid;
- and
- (b) a vector genome packaged in the AAV capsid of (a), wherein the vector genome comprises inverted terminal repeats (ITR) and a nucleic acid sequence encoding a functional human Arylsulfatase A (hARSA) operably linked to regulatory sequences which direct the hARSA expression, wherein the hARSA coding sequence comprises a nucleic acid sequence encoding a signal peptide and a sequence of nucleotide (nt) 55 to nt 1521 of SEQ ID NO:
- 1, or a sequence at least 95% identical thereto which encodes a functional hARSA.
An rAAV comprising:
- (a) an AAVhu68 capsid and
- (b) a vector genome in the AAVhu68 capsid, the vector genome comprising:
- an AAV inverted terminal (ITR),
- an expression cassette comprising an enhancer, a promoter, an intron, an hARSA coding sequence which is at least 99% identical to nt 1935 to 3506 of SEQ ID NO:
- 5, a polyadenylation signal, and
- an AAV ITR.
Dependencies are inferred from the claim text.