Gene therapy for ceroid lipofuscinoses
AssigneeThe Trustees of the University of Pennsylvania
InventorsJames M. Wilson, Nathan Katz, Christian Hinderer, Juliette Hordeaux
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Abstract
Provided herein are methods and compositions for treatment of Batten disease. Such compositions include a recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising (a) an AAV inverted terminal repeat (ITR) sequence; (b) a promoter; (c) a CLN2 coding sequence encoding a human TPP1; (d) an AAV 3′ ITR.
Claims47
A recombinant adeno-associated virus (rAAV), comprising an AAV serotype 9 (AAV9) capsid, wherein the rAAV comprises a vector genome packaged within the capsid, wherein the vector genome comprises:
- (a) an AAV2 5′ inverted terminal repeat (ITR) sequence;
- (b) a promoter;
- (c) a CLN2 coding sequence encoding a human tripeptidyl peptidase 1 (TPP1);
- and
- (d) an AAV2 3′ ITR sequence,
- wherein the CLN2 coding sequence shares 95% or greater identity with the nucleotide sequence set forth in SEQ ID NO:
- 3.
A recombinant adeno-associated virus (rAAV), comprising an AAV serotype 9 (AAV9) capsid or a variant thereof, wherein the rAAV comprises a vector genome packaged within the AAV9 capsid or variant thereof, wherein the vector genome comprises:
- (a) an AAV2 5′ inverted terminal repeat (ITR) sequence;
- (b) a CBA promoter;
- (c) a CLN2 coding sequence comprising nucleotides 1 to 1689 of SEQ ID NO:
- 3 encoding a human TPP1;
- (d) a polyA;
- and
- (e) an AAV2 3′ ITR sequence.
A recombinant adeno-associated virus (rAAV), comprising an AAV9 capsid or variant thereof, wherein the rAAV comprises a vector genome packaged within the AAV9 capsid or variant thereof, wherein the vector genome comprises:
- (a) an AAV2 5′ inverted terminal repeat (ITR) sequence;
- (b) a promoter;
- (c) a CLN2 coding sequence encoding a human TPP1;
- and
- (d) an AAV2 3′ ITR sequence,
- wherein the CLN2 coding sequence shares 95% or greater identity with the nucleotide sequence set forth in SEQ ID NO:
- 3, and
- wherein the AAV9 capsid or variant thereof comprises capsid proteins having an amino acid sequence that shares 95% or greater identity with the amino acid sequence set forth in SEQ ID NO:
- 6.
A recombinant nucleic acid molecule comprising an expression cassette comprising a CLN2 coding sequence, wherein the CLN2 coding sequence comprises nucleotides 1 to 1689 of SEQ ID NO:
- 3.
An aqueous suspension comprising an aqueous suspending liquid and about 1×109 to about 1×1015 genome copies or viral particles of the recombinant adeno-associated virus (rAAV), said rAAV having an AAV9 capsid, and having packaged therein a vector genome comprising:
- (a) an AAV2 5′ inverted terminal repeat (ITR) sequence;
- (b) a promoter;
- (c) a CLN2 coding sequence encoding a human tripeptidyl peptidase 1 (TPP1);
- and
- (d) an AAV2 3′ ITR sequence,
- wherein the CLN2 coding sequence shares 95% or greater identity with the nucleotide sequence set forth in SEQ ID NO:
- 3.
Dependencies are inferred from the claim text.