GENE THERAPY FOR JUVENILE BATTEN DISEASE
Compositions and methods for the treatment of Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), also known as Juvenile Batten Disease, are provided herein. In certain embodiments the compositions include but are not limited to adeno-associated viral (AAV) constructs, including self-complementary adeno-associated viral (sc-AAV) constructs, that express the human gene CLN3 (or a CLN3 cDNA).
1 .- 70 . (canceled)
71 . A composition comprising a recombinant adeno-associated viral (rAAV) vector comprising a polynucleotide sequence encoding CLN3 operably linked to a methyl-CPG binding protein 2 (MeCP2) promoter, wherein the rAAV vector is of a serotype selected from AAV1, AAV2, AAV4, AAV5, AAV6, AAV8, or AAV9.
72 . The composition of claim 71 , wherein the CLN3 is a human CLN3.
73 . The composition of claim 71 , wherein the rAAV vector comprises a polynucleotide sequence of SEQ ID NO: 2.
74 . The composition of claim 71 , wherein the serotype is AAV9.
75 . The composition of claim 71 , wherein the serotype is AAV2.
76 . The composition of claim 71 , wherein the rAAV vector is single stranded or self-complimentary.
77 . The composition of claim 71 , wherein the rAAV vector is a self-complementary AAV9 vector.
78 . The composition of claim 71 , wherein the rAAV vector further comprises a 5′UTR/intron selected from a SV40, a minimal SV40 intron, or CBA-MVM.
79 . The composition of claim 71 , wherein the rAAV vector further comprises a polyadenylation signal selected from a bovine growth hormone polyadenylation sequence, a SV40 late polyadenylation sequence, a SV40 early polyadenylation sequence.
80 . The composition of claim 79 , wherein the polyadenylation signal comprises a nucleic acid sequence of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, or SEQ ID NO: 6.
81 . The composition of claim 71 , wherein the rAAV vector further comprises a posttranslational regulatory element.
82 . The composition of claim 81 , wherein the posttranslational regulatory element is selected from a Woodchuck Post-transcriptional Regulatory Element (WPRE), a WPRE2, or a WPRE3.
83 . The composition of claim 81 , wherein the posttranslational regulatory element is hepatitis B virus posttranscriptional regulatory element (HPRE).
84 . The composition of claim 71 , wherein the rAAV vector is a self-complementary serotype AAV9 vector comprising a polynucleotide sequence encoding CLN3 that comprises a nucleic acid sequence of SEQ ID NO: 11 operably linked to the MeCP2 promoter.
85 . The composition of claim 71 , wherein the rAAV vector comprises a minimal SV40 intron.
86 . The composition of claim 71 , wherein the composition further comprises a pharmaceutically acceptable carrier or diluent.
87 . A recombinant adeno-associated viral (rAAV) vector comprising a polynucleotide sequence encoding CLN3 operably linked to a promoter selected from a methyl-CPG binding protein 2 (MeCP2) promoter, a β-glucuronidase (GUSB) promoter, a neuron-specific enolase (NSE) promoter, a synapsin promoter, an oligodendrocyte transcription factor 1 (Olig1) promoter, a chondroitin sulfate proteoglycan (Cspg4) promoter, a 2′,3′-Cyclic-nucleotide 3 '-phosphodiesterase (CNP) promoter, or a glial fibrillary acidic protein (GFAP) promoter, wherein the rAAV vector is of a serotype selected from AAV1, AAV2, AAV4, AAV5, AAV6, AAV8, or AAV9.
88 . A host cell comprising the rAAV vector of claim 87 .